General Information of the Disease (ID: DIS00062)
Name
Osteosarcoma
ICD
ICD-11: 2B51
Resistance Map
Type(s) of Resistant Mechanism of This Disease
  DISM: Drug Inactivation by Structure Modification
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  IDUE: Irregularity in Drug Uptake and Drug Efflux
  RTDM: Regulation by the Disease Microenvironment
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Drug
Approved Drug(s)
17 drug(s) in total
Click to Show/Hide the Full List of Drugs
Bortezomib
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-101 [1]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Bortezomib
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description miR-101 functions as an endogenous proteasome inhibitor by targeting POMP. Targeting POMP is essential for cell growth suppression by miR-101. High miR-101 levels have good outcomes for ERalpha-positive breast cancer patients. Targeting POMP inhibits tumor progression and overcomes resistance to bortezomib.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Proteasome maturation protein (POMP) [1]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Bortezomib
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description miR-101 functions as an endogenous proteasome inhibitor by targeting POMP. Targeting POMP is essential for cell growth suppression by miR-101. High miR-101 levels have good outcomes for ERalpha-positive breast cancer patients. Targeting POMP inhibits tumor progression and overcomes resistance to bortezomib.
Carboplatin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-34a-5p [2]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Carboplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Annexin V-FITC/propidium iodide (PI) staining assay
Mechanism Description The miR34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene.
Key Molecule: hsa-miR-199a-3p [3]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Carboplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description The Ak4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance.
Key Molecule: hsa-miR-34a-5p [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Carboplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Type-1 angiotensin II receptor (AGTR1) [2]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Carboplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Annexin V-FITC/propidium iodide (PI) staining assay
Mechanism Description The miR34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene.
Key Molecule: Adenylate kinase 4 (AK4) [3]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Carboplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis; RIP assay; Luciferase reporter assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description The Ak4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance.
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Carboplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
Cisplatin
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: OIP5 antisense RNA 1 (OIP5-AS1) [5]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT/mTOR signaling pathway Activation hsa04151
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description OIP5-AS1 regulates cisplatin resistance by activating the PI3k/AkT/mTOR signaling pathway.
Key Molecule: hsa-miR-340-5p [5]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT/mTOR signaling pathway Activation hsa04151
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description OIP5-AS1 regulates cisplatin resistance by activating the PI3k/AkT/mTOR signaling pathway.
Key Molecule: hsa-miR-34a-5p [2], [6]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ATF2/ATF3/ATF4 signaling pathway Inhibition hsa04915
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Annexin V-FITC/propidium iodide (PI) staining assay
Mechanism Description The miR34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene. And miR34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene.
Key Molecule: Delta-like protein 1 (DLL1) [6]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ATF2/ATF3/ATF4 signaling pathway Inhibition hsa04915
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
IC50 assay; Flow cytometric analysis
Mechanism Description miR34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene. The activity of the ATF2/ATF3/ATF4 pathway was reduced in the miR34a-5p mimic-transfected G-292 cells but increased in the miR34a-5p antagomiRtransfected SJSA-1 cells, hence the ATF2/ATF3/ATF4 pathway was validated to be involved in the OS chemoresistance mediated by miR34a-5p.
Key Molecule: hsa-miR-199a-3p [3]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description The Ak4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance.
Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [7]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation BCL2/cyclin D1 signaling pathway Inhibition hsa04210
Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description The miR-34c inhibitor restored the BCL-2 and cyclin D1 levels in MG63 and HOS cell line, which implicated that NEAT1 inhibited the tumor suppressor miR-34c and up-regulated cell survival signals for the development of OS.
Key Molecule: hsa-mir-377 [8]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
MG63/CDDP cells Bone Homo sapiens (Human) CVCL_0426
SAOS-2/CDDP cells Bone Homo sapiens (Human) CVCL_0548
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description XIAP overexpression greatly cancelled the apoptosis promoting the effect of miR377 in Saos-2/CDDP cell.
Key Molecule: hsa_circ_PVT1 [9]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell colony Activation hsa05200
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
KHOS cells Bone Homo sapiens (Human) CVCL_2546
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Colony formation assay
Mechanism Description CircPVT1 knockdown reduces the expression of classical multidrug resistance related gene-ABCB1 in OS cells.
Key Molecule: hsa-mir-340 [10]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description Overexpression of ZEB1 reversed the miR-340-induced alleviation of chemoresistance in drug-resistant OS cells.
Key Molecule: hsa-miR-34a-5p [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
Key Molecule: hsa-miR-146b-5p [11]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
Wnt/Beta-catenin signaling pathway Regulation hsa04310
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
hFOB1.19 cells Fetal bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-146b-5p was highly expressed in human osteosarcoma tissues and an elevated expression of miR-146b-5p was observed in human osteosarcoma tissues after chemotherapy. Furthermore, it was shown that miR-146b-5p overexpression promoted migration and invasiveness. miR-146b-5p overexpression also increased resistance to chemotherapy. Moreover, knockdown of miR-146b-5p substantially inhibited migration and invasion of osteosarcoma cells as well as rendered them significantly more sensitive to chemotherapy. Results of western blot assay indicated that miR-146b-5p increased MMP-16 protein expression and showed a decrease of ZNRF3 protein. Whereas, IWR-1-endo, an inhibitor of Wnt/beta-catenin, suppressed the decrease in apoptosis of osteosarcoma cells caused by miR-146b-5p overexpression. These results indicated that miR-146b-5p promoted proliferation, migration and invasiveness.
Key Molecule: hsa-mir-33a [12]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
TUNEL assay
Mechanism Description miR-33a is up-regulated in chemoresistant OS and that the miR-33a level is negatively correlated with the TWIST protein level in OS. miR-33a promotes OS cell resistance to cisplatin by down-regulating TWIST.
Key Molecule: hsa-mir-221 [13]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
PI3K/AKT signaling pathway Regulation hsa04151
In Vitro Model SOSP-9607 cells Bones Homo sapiens (Human) CVCL_4V80
SOSP-9901 cells Bones Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration
qRT-PCR; RT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-221 induce cell survival and cisplatin resistance in human osteosarcoma at least partly through targeting the PI3k/PTEN/Akt pathway.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [9]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell colony Activation hsa05200
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
KHOS cells Bone Homo sapiens (Human) CVCL_2546
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Colony formation assay
Mechanism Description CircPVT1 knockdown reduces the expression of classical multidrug resistance related gene-ABCB1 in OS cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interleukin-24 (IL24) [14]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ZBTB7A/LINC00473/IL24 signaling pathway Regulation hsa04630
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR; Dual-Luciferase reporter assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description LINC00473 promoted the activity of IL24 promoter and elevated IL24 expression. LINC00473 interacts with the transcript factor C/EBPbeta, facilitating its binding to the promoter of IL24, leading to decrease chemoresistance. The ZBTB7A-LINC00473-IL24 signaling axis plays an important role in regulating osteosarcoma chemoresistance.
Key Molecule: Zinc finger and BTB domain-containing protein 7A (ZBTB7A) [14]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ZBTB7A/LINC00473/IL24 signaling pathway Regulation hsa04630
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description Elevated ZBTB7A inhibits cisplatin-induced apoptosis by repressing LINC00473 expression. The ZBTB7A-LINC00473-IL24 signaling axis plays an important role in regulating osteosarcoma chemoresistance.
Key Molecule: Type-1 angiotensin II receptor (AGTR1) [2]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Annexin V-FITC/propidium iodide (PI) staining assay
Mechanism Description The miR34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene.
Key Molecule: Interferon-induced protein with tetratricopeptide repeats 2 (IFIT2) [15]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell colony Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Ckk-8 assay; Colony formation assay; Annexin V-FITC staining assay
Mechanism Description Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR645-IFIT2 axis. LINC00161 upregulated IFIT2 expression via miR645.
Key Molecule: Adenylate kinase 4 (AK4) [3]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis; RIP assay; Luciferase reporter assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description The Ak4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [7]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation BCL2/cyclin D1 signaling pathway Inhibition hsa04210
Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description The miR-34c inhibitor restored the BCL-2 and cyclin D1 levels in MG63 and HOS cell line, which implicated that NEAT1 inhibited the tumor suppressor miR-34c and up-regulated cell survival signals for the development of OS.
Key Molecule: G1/S-specific cyclin-D1 (CCND1) [7]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation BCL2/cyclin D1 signaling pathway Inhibition hsa04210
Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description The miR-34c inhibitor restored the BCL-2 and cyclin D1 levels in MG63 and HOS cell line, which implicated that NEAT1 inhibited the tumor suppressor miR-34c and up-regulated cell survival signals for the development of OS.
Key Molecule: E3 ubiquitin-protein ligase XIAP (XIAP) [8]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
MG63/CDDP cells Bone Homo sapiens (Human) CVCL_0426
SAOS-2/CDDP cells Bone Homo sapiens (Human) CVCL_0548
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description XIAP overexpression greatly cancelled the apoptosis promoting the effect of miR377 in Saos-2/CDDP cell.
Key Molecule: Zinc finger E-box-binding homeobox 1 (ZEB1) [10]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description Overexpression of ZEB1 reversed the miR-340-induced alleviation of chemoresistance in drug-resistant OS cells.
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
Key Molecule: E3 ubiquitin-protein ligase ZNRF3 (ZNRF3) [11]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
Wnt/Beta-catenin signaling pathway Regulation hsa04310
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
hFOB1.19 cells Fetal bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-146b-5p was highly expressed in human osteosarcoma tissues and an elevated expression of miR-146b-5p was observed in human osteosarcoma tissues after chemotherapy. Furthermore, it was shown that miR-146b-5p overexpression promoted migration and invasiveness. miR-146b-5p overexpression also increased resistance to chemotherapy. Moreover, knockdown of miR-146b-5p substantially inhibited migration and invasion of osteosarcoma cells as well as rendered them significantly more sensitive to chemotherapy. Results of western blot assay indicated that miR-146b-5p increased MMP-16 protein expression and showed a decrease of ZNRF3 protein. Whereas, IWR-1-endo, an inhibitor of Wnt/beta-catenin, suppressed the decrease in apoptosis of osteosarcoma cells caused by miR-146b-5p overexpression. These results indicated that miR-146b-5p promoted proliferation, migration and invasiveness.
Key Molecule: Twist-related protein 1 (TWST1) [12]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
TUNEL assay
Mechanism Description miR-33a is up-regulated in chemoresistant OS and that the miR-33a level is negatively correlated with the TWIST protein level in OS. miR-33a promotes OS cell resistance to cisplatin by down-regulating TWIST.
Key Molecule: Phosphatase and tensin homolog (PTEN) [13]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Cisplatin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
PI3K/AKT signaling pathway Regulation hsa04151
In Vitro Model SOSP-9607 cells Bones Homo sapiens (Human) CVCL_4V80
SOSP-9901 cells Bones Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-221 induce cell survival and cisplatin resistance in human osteosarcoma at least partly through targeting the PI3k/PTEN/Akt pathway.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-34 [16]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Bim signaling pathway Activation hsa05206
c-Myc signaling pathway Activation hsa05230
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
MTT assay; Flow cytometric analysis
Mechanism Description miR34a increases cisplatin sensitivity of osteosarcoma cells in vitro through up-regulation of c-Myc and Bim signal.
Key Molecule: hsa-mir-200c [17]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
RT-PCR; RT-qPCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometric analysis; Caspase-3 Activity Assay
Mechanism Description miR200c regulates tumor growth and chemosensitivity to cisplatin in osteosarcoma by targeting AkT2 and inhibiting the activity of cell proliferation and cell migration.
Key Molecule: Long non-protein coding RNA (LINC00473) [14]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ZBTB7A/LINC00473/IL24 signaling pathway Regulation hsa04630
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description LINC00473 promoted the activity of IL24 promoter and elevated IL24 expression. LINC00473 interacts with the transcript factor C/EBPbeta, facilitating its binding to the promoter of IL24, leading to decrease chemoresistance. The ZBTB7A-LINC00473-IL24 signaling axis plays an important role in regulating osteosarcoma chemoresistance.
Key Molecule: hsa-mir-491 [18]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
RT-PCR; RT-qPCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description Overexpression of miR491 inhibits chemoresistance and suppresses OS cell lung metastasis, whereas it enhances cisplatin (CDDP)-induced tumor growth inhibition and apoptosis, miR491 exerts its role by directly targeting alphaB-crystallin (CRYAB) in OS.
Key Molecule: hsa-miR-340-5p [19]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
MG63/CDDP cells Bone Homo sapiens (Human) CVCL_0426
SAOS-2/CDDP cells Bone Homo sapiens (Human) CVCL_0548
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Annexin V-FITC apoptosis assay
Mechanism Description microRNA-340-5p modulates cisplatin resistance by targeting LPAATbeta in osteosarcoma.
Key Molecule: hsa-mir-410 [20]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description microRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma, miR410 directly decreased ATG16L1 expression by targeting its 3'-untranslated region.
Key Molecule: hsa-miR-199a-5p [21]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR199a-5p directly targeted Beclin1 and negatively mediated Beclin1 expression at a post-transcriptional level, microRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of autophagy in osteosarcoma cells.
Key Molecule: hsa-miR-422a [22]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFOB cells Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
MTT assay; Flow cytometric analysis of apoptosis; Transwell assay
Mechanism Description Overexpression of miR422a inhibits cell proliferation and invasion, and enhances chemosensitivity by directly targeting TGFbeta2 in osteosarcoma cells.
Key Molecule: hsa-mir-381 [23]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation mTOR signaling pathway Regulation hsa04150
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Matrigel chamber invasion assay
Mechanism Description There is a strong negative correlation between the expression of miR381 and LRRC4, suppressing the expression of miR381 increases the sensitivity of OS cells to chemotherapeutic drugs through the LRRC4-mediated mTOR pathway.
Key Molecule: Long non-protein coding RNA 161 (LINC00161) [15]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Ckk-8 assay; Colony formation assay; Annexin V-FITC staining assay
Mechanism Description Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR645-IFIT2 axis. LINC00161 acted as a miR645 sponge and inhibited its activity.
Key Molecule: hsa-miR-645 [15]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Ckk-8 assay; Colony formation assay; Annexin V-FITC staining assay
Mechanism Description Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR645-IFIT2 axis. LINC00161 acted as a miR645 sponge and inhibited its activity.
Key Molecule: CDKN2B antisense RNA 1 (CDKN2B-AS1) [24]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell colony Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description ANRIL-silenced cells were more sensitive to cisplatin and the expression level of miR-125a-5p was elevated in ANRIL-silenced cells.
Key Molecule: hsa-miR-125a-5p [24]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell colony Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description ANRIL-silenced cells were more sensitive to cisplatin and the expression level of miR-125a-5p was elevated in ANRIL-silenced cells.
Key Molecule: hsa-mir-92a [25]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell viability Inhibition hsa05200
Notch1 signaling pathway Regulation hsa04330
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
HOS cells Bone Homo sapiens (Human) CVCL_0312
HFOB cells Bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay; Transwell assay
Mechanism Description miR-92a inhibited cell growth, migration, and enhanced cisplatin sensitivity of OS cell by downregulating Notch1.
Key Molecule: hsa-mir-34c [7]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation BCL2/cyclin D1 signaling pathway Inhibition hsa04210
Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description The miR-34c inhibitor restored the BCL-2 and cyclin D1 levels in MG63 and HOS cell line, which implicated that NEAT1 inhibited the tumor suppressor miR-34c and up-regulated cell survival signals for the development of OS.
Key Molecule: hsa-mir-22 [26]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description miR-22 overexpression sensitizes MG-63 cells to cisplatin treatment and reduces the expression of S100A11.
Key Molecule: hsa-mir-223 [27]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
JNk signaling pathway Activation hsa04010
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
HOS cells Bone Homo sapiens (Human) CVCL_0312
Sk-ES-1 cells Bone Homo sapiens (Human) CVCL_0627
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-223 overexpression could sensitize OS cell lines to CDDP and Hsp70 protein levels were remarkably reduced by miR-223 overexpression whereas increased by miR-223 inhibition.
Key Molecule: hsa-mir-21 [28]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
HLNG cells Bone marrow Homo sapiens (Human) N.A.
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Northern blot analysis
Experiment for
Drug Resistance
Scratch assay
Mechanism Description miR-21 regulatory network plays a role in tumorigenesis of osteosarcoma. Its expression facilitates cell proliferation and decreases cellular sensitivity towards cisplatin. Both effects can be rescued by Spry2, a target protein downregulated by increased miR-21 levels.
Key Molecule: hsa-mir-138 [29]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
miR138/EZH2 signaling pathway Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
In Vivo Model BALB/c nu/nu nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description miR-138 acts as a tumor suppressor in osteosarcoma, inhibiting cell proliferation, migration, and invasion by downregulating EZH2 expression. Mir-138 overexpression also enhances osteosarcoma cell chemosensitivity to cisplatin by targeting EZH2.
Key Molecule: hsa-mir-125b [30]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
p53/p38/MAPK signaling pathway Regulation hsa04010
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description Overexpression of miR-125b inhibited proliferation, migration, and invasion of OS cells and reduced the chemotherapy resistance of OS cells to cisplatin by targeting Bcl-2.
Key Molecule: hsa-mir-382 [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: hsa-mir-29b [32]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model 3AB-OS CSC cells Bone marrow Homo sapiens (Human) CVCL_LM95
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Trypan blue assay; Flow cytometry assay
Mechanism Description miR-29b-1 overexpression sensitized 3AB-OS cells to chemotherapeutic drug-induced apoptosis miR-29b-1 negatively regulated the expression of Bcl-2.
Key Molecule: hsa-mir-103 [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: hsa-miR-107 [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: hsa-mir-96 [34]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: RAC-beta serine/threonine-protein kinase (AKT2) [17]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Luciferase reporter assay
Experiment for
Drug Resistance
CCK8 assay; Flow cytometric analysis; Caspase-3 Activity Assay
Mechanism Description miR200c regulates tumor growth and chemosensitivity to cisplatin in osteosarcoma by targeting AkT2 and inhibiting the activity of cell proliferation and cell migration.
Key Molecule: Alpha-crystallin B chain (CRYAB) [18]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR; Luciferase reporter assay; Western blot analysis; Western blot analysis; Immunohistochemistry assay
Experiment for
Drug Resistance
MTT assay
Mechanism Description Overexpression of miR491 inhibits chemoresistance and suppresses OS cell lung metastasis, whereas it enhances cisplatin (CDDP)-induced tumor growth inhibition and apoptosis, miR491 exerts its role by directly targeting alphaB-crystallin (CRYAB) in OS.
Key Molecule: Lysophosphatidic acid acyltransferase beta (AGPAT2) [19]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
MG63/CDDP cells Bone Homo sapiens (Human) CVCL_0426
SAOS-2/CDDP cells Bone Homo sapiens (Human) CVCL_0548
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Annexin V-FITC apoptosis assay
Mechanism Description microRNA-340-5p modulates cisplatin resistance by targeting LPAATbeta in osteosarcoma.
Key Molecule: Autophagy-related protein 16-1 (ATG16L1) [20]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
Luciferase reporter assay; Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description microRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma, miR410 directly decreased ATG16L1 expression by targeting its 3'-untranslated region.
Key Molecule: Beclin-1 (BECN1) [21]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR199a-5p directly targeted Beclin1 and negatively mediated Beclin1 expression at a post-transcriptional level, microRNA-199a-5p inhibits cisplatin-induced drug resistance via inhibition of autophagy in osteosarcoma cells.
Key Molecule: Transforming growth factor beta-2 proprotein (TGFB2) [22]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFOB cells Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
Western blot analysis; Dual luciferase activity assay
Experiment for
Drug Resistance
MTT assay; Flow cytometric analysis of apoptosis; Transwell assay
Mechanism Description Overexpression of miR422a inhibits cell proliferation and invasion, and enhances chemosensitivity by directly targeting TGFbeta2 in osteosarcoma cells.
Key Molecule: Leucine-rich repeat-containing protein 4 (LRRC4) [23]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation mTOR signaling pathway Regulation hsa04150
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Matrigel chamber invasion assay
Mechanism Description There is a strong negative correlation between the expression of miR381 and LRRC4, suppressing the expression of miR381 increases the sensitivity of OS cells to chemotherapeutic drugs through the LRRC4-mediated mTOR pathway.
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [25]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell viability Inhibition hsa05200
Notch1 signaling pathway Regulation hsa04330
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
HOS cells Bone Homo sapiens (Human) CVCL_0312
HFOB cells Bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay; Transwell assay
Mechanism Description miR-92a inhibited cell growth, migration, and enhanced cisplatin sensitivity of OS cell by downregulating Notch1.
Key Molecule: Nuclear paraspeckle assembly transcript 1 (NEAT1) [7]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation BCL2/cyclin D1 signaling pathway Inhibition hsa04210
Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description The miR-34c inhibitor restored the BCL-2 and cyclin D1 levels in MG63 and HOS cell line, which implicated that NEAT1 inhibited the tumor suppressor miR-34c and up-regulated cell survival signals for the development of OS.
Key Molecule: Protein S100-A11 (S100A11) [26]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description miR-22 overexpression sensitizes MG-63 cells to cisplatin treatment and reduces the expression of S100A11.
Key Molecule: Heat shock 70 kDa protein 1A (HSP70) [27]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell viability Inhibition hsa05200
JNk signaling pathway Activation hsa04010
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
HOS cells Bone Homo sapiens (Human) CVCL_0312
Sk-ES-1 cells Bone Homo sapiens (Human) CVCL_0627
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-223 overexpression could sensitize OS cell lines to CDDP and Hsp70 protein levels were remarkably reduced by miR-223 overexpression whereas increased by miR-223 inhibition.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [30], [32]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
p53/p38/MAPK signaling pathway Regulation hsa04010
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
3AB-OS CSC cells Bone marrow Homo sapiens (Human) CVCL_LM95
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
RT-PCR; Western blot analysis
Experiment for
Drug Resistance
Trypan blue assay; Flow cytometry assay; CCK8 assay
Mechanism Description miR-29b-1 overexpression sensitized 3AB-OS cells to chemotherapeutic drug-induced apoptosis miR-29b-1 negatively regulated the expression of Bcl-2. Overexpression of miR-125b inhibited proliferation, migration, and invasion of OS cells and reduced the chemotherapy resistance of OS cells to cisplatin by targeting Bcl-2.
Key Molecule: Protein sprouty homolog 2 (SPRY2) [28]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
HLNG cells Bone marrow Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration
Northern blotting
Experiment for
Drug Resistance
Scratch assay
Mechanism Description miR-21 regulatory network plays a role in tumorigenesis of osteosarcoma. Its expression facilitates cell proliferation and decreases cellular sensitivity towards cisplatin. Both effects can be rescued by Spry2, a target protein downregulated by increased miR-21 levels.
Key Molecule: Histone-lysine N-methyltransferase EZH2 (EZH2) [29]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
miR138/EZH2 signaling pathway Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
Experiment for
Molecule Alteration
Western blot analysis; Flow cytometric assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description miR-138 acts as a tumor suppressor in osteosarcoma, inhibiting cell proliferation, migration, and invasion by downregulating EZH2 expression. Mir-138 overexpression also enhances osteosarcoma cell chemosensitivity to cisplatin by targeting EZH2.
Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: Krueppel-like factor 12 (KLF12) [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: DNA repair protein RAD51 homolog 1 (RAD51) [33], [34]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization. And overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.
Key Molecule: DNA repair protein RAD51 homolog 4 (RAD51D) [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: DNA repair protein REV1 (REV1) [34]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Cisplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Overexpression of miR-96 in human cancer cells reduces the levels of RAD51 and REV1 and impacts the cellular response to agents that cause DNA damage.
Decitabine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Cyclin-dependent kinase inhibitor 2A (CDKN2A) [35]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Decitabine
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
HOTAIR-miR126-DNMT1-CDkN2A axis Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
NHOst cells Bone Homo sapiens (Human) N.A.
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
RT-qPCR; ChIP assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description HOTAIR represses the expression of CDkN2A through inhibiting the promoter activity of CDkN2A by RNA hypermethylation. HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDkN2A axis.
Key Molecule: HOX transcript antisense RNA (HOTAIR) [35]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Decitabine
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
HOTAIR-miR126-DNMT1-CDkN2A axis Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
NHOst cells Bone Homo sapiens (Human) N.A.
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description HOTAIR represses the expression of CDkN2A through inhibiting the promoter activity of CDkN2A by RNA hypermethylation. HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDkN2A axis.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: DNA (cytosine-5)-methyltransferase 1 (DNMT1) [35]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Decitabine
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
HOTAIR-miR126-DNMT1-CDkN2A axis Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
NHOst cells Bone Homo sapiens (Human) N.A.
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
RT-qPCR; Western blot analysis; ChIP assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description HOTAIR activates the expression of DNMT1 through repressing miR126, which is the negative regulator of DNMT1. HOTAIR depletion increases the sensibility of OS cells to DNMT1 inhibitor through regulating the viability and apoptosis of OS cells via HOTAIR-miR126-DNMT1-CDkN2A axis.
Doxorubicin
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-152 [36]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
c-Met/PI3K/AKT signaling pathway Activation hsa01521
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay; Soft agar assay
Mechanism Description LncRNAPVT1 targets miR-152 to enhance chemoresistance of osteosarcoma to doxorubicin through activating c-MET/PI3k/AkT pathway.
Key Molecule: Pvt1 oncogene (PVT1) [36]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
c-Met/PI3K/AKT signaling pathway Activation hsa01521
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay; Soft agar assay
Mechanism Description LncRNAPVT1 targets miR-152 to enhance chemoresistance of osteosarcoma to doxorubicin through activating c-MET/PI3k/AkT pathway.
Key Molecule: hsa-miR-34a-5p [2], [6]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ATF2/ATF3/ATF4 signaling pathway Inhibition hsa04915
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Annexin V-FITC/propidium iodide (PI) staining assay
Mechanism Description The miR34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene. And miR34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene.
Key Molecule: hsa-miR-20a-5p [37]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description miR20a-5p modulates multi-drug resistance by repressing SDC2 expression in OS cells.
Key Molecule: hsa-mir-375 [38]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Multivariate analysis of overall survival or disease-free survival assay
Mechanism Description miR375 overexpression could increase the cisplatin sensitivity of human gastric cancer cells by regulating ERBB2.
Key Molecule: hsa-miR-3182 [39]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation ODRUL/miR3182/MMP2 signaling pathway Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Dual Luciferase Reporter Assay; PCR
Experiment for
Drug Resistance
Wound Healing Assay; Colony Formation Assay; CCK8 Assay
Mechanism Description LncRNA ODRUL Contributes to Osteosarcoma Progression through the miR3182/MMP2 Axis. miR3182 expression and function are inversely correlated with ODRUL expression in vitro and in vivo, miR3182 negatively regulated the mRNA level and the protein level of MMP2 expression. ODRUL could directly interact with miR3182 and upregulate MMP2 expression via its competing endogenous RNA activity on miR3182 at the posttranscriptional level.
Key Molecule: FOXC2 antisense RNA 1 (FOXC2-AS1) [39]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation ODRUL/miR3182/MMP2 signaling pathway Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
143B cells Bone Homo sapiens (Human) CVCL_2270
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
PCR
Experiment for
Drug Resistance
Wound Healing Assay; Colony Formation Assay; CCK8 Assay
Mechanism Description LncRNA ODRUL Contributes to Osteosarcoma Progression through the miR3182/MMP2 Axis. miR3182 expression and function are inversely correlated with ODRUL expression in vitro and in vivo, miR3182 negatively regulated the mRNA level and the protein level of MMP2 expression. ODRUL could directly interact with miR3182 and upregulate MMP2 expression via its competing endogenous RNA activity on miR3182 at the posttranscriptional level.
Key Molecule: hsa-miR-140-5p [40]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell autophagy Activation hsa04140
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
hFOB1.19 cells Fetal bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
IC50 assay; Flow cytometric analysis
Mechanism Description miR140-5p/HMGN5/autophagy regulatory loop plays a critical role in chemoresistance in osteosarcoma, miR 140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy.
Key Molecule: FOXC2 antisense RNA 1 (FOXC2-AS1) [41]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Colony formation assay
Mechanism Description Antisense LncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2. FOXC2-AS1 contributes to doxorubicin resistance by increasing FOXC2 and further facilitating ABCB1.
Key Molecule: Delta-like protein 1 (DLL1) [6]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ATF2/ATF3/ATF4 signaling pathway Inhibition hsa04915
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
IC50 assay; Flow cytometric analysis
Mechanism Description miR34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene. The activity of the ATF2/ATF3/ATF4 pathway was reduced in the miR34a-5p mimic-transfected G-292 cells but increased in the miR34a-5p antagomiRtransfected SJSA-1 cells, hence the ATF2/ATF3/ATF4 pathway was validated to be involved in the OS chemoresistance mediated by miR34a-5p.
Key Molecule: Small nucleolar RNA host gene 12 (SNHG12) [42]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description The up-regulation of MCL1 reversed the sensitivity of doxorubicin induced by miR-320a mimics and knockdown of SNHG12.
Key Molecule: hsa-mir-320 [42]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description The up-regulation of MCL1 reversed the sensitivity of doxorubicin induced by miR-320a mimics and knockdown of SNHG12.
Key Molecule: hsa-miR-199a-3p [3]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description The Ak4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance.
Key Molecule: hsa_circ_PVT1 [9]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell colony Activation hsa05200
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
KHOS cells Bone Homo sapiens (Human) CVCL_2546
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Colony formation assay
Mechanism Description CircPVT1 knockdown reduces the expression of classical multidrug resistance related gene-ABCB1 in OS cells.
Key Molecule: hsa-miR-184 [43]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/BCL2 signaling pathway Regulation hsa04933
Cell apoptosis Activation hsa04210
NF-kappaB signaling pathway Regulation hsa04064
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description microRNA-184 modulates doxorubicin resistance in osteosarcoma cells by targeting BCL2L1 and enhancing the level of it.
Key Molecule: hsa-miR-34a-5p [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
Key Molecule: hsa-mir-30a [44]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description Down-regulation of miR-30a contributed to chemoresistance of osteosarcoma cells through regulating autophagy. Furthermore, to investigate the mechanism of miR-130a in regulating autophagy, bioinformatics analysis was performed. The results showed that the 3'-UTR region of Beclin-1 were the binding sites for miR-30a. Consistently, previous studies demonstrated that Beclin-1 was the directly target of miR-30a.
Key Molecule: hsa-miR-146b-5p [11]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
Cell viability Activation hsa05200
Wnt/Beta-catenin signaling pathway Regulation hsa04310
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
hFOB1.19 cells Fetal bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-146b-5p was highly expressed in human osteosarcoma tissues and an elevated expression of miR-146b-5p was observed in human osteosarcoma tissues after chemotherapy. Furthermore, it was shown that miR-146b-5p overexpression promoted migration and invasiveness. miR-146b-5p overexpression also increased resistance to chemotherapy. Moreover, knockdown of miR-146b-5p substantially inhibited migration and invasion of osteosarcoma cells as well as rendered them significantly more sensitive to chemotherapy. Results of western blot assay indicated that miR-146b-5p increased MMP-16 protein expression and showed a decrease of ZNRF3 protein. Whereas, IWR-1-endo, an inhibitor of Wnt/beta-catenin, suppressed the decrease in apoptosis of osteosarcoma cells caused by miR-146b-5p overexpression. These results indicated that miR-146b-5p promoted proliferation, migration and invasiveness.
Key Molecule: hsa-mir-143 [45]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model NOD-SCID IL2-rgamma -null (NSG) mouse engraftment model Mus musculus
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
MTT assay; Matrigel colony formation assay; Hoechst33342 staining assay
Mechanism Description In chemoresistant SAOS-2 and U2OS osteosarcomas cells, miR-143 levels were significantly downregulated and accompanied by increases in ATG2B, Bcl-2, and/or LC3-II protein levels, high rate of ALDH1+CD133+ cells, and an increase in Matrigel colony formation ability. H2O2 upregulated p53 and miR-143, but downregulated ATG2B, Bcl-2, and LC3-I expression in U2OS cells (wild-type p53) but not in SAOS-2 (p53-null) cells. Forced miR-143 expression significantly reversed chemoresistance as well as downregulation of ATG2B, LC3-I, and Bcl-2 expression in SAOS-2- and U2OS-resistant cells. Forced miR-143 expression significantly inhibited tumor growth in xenograft SAOS-2-Dox and U2OS-Dox animal models. Loss of miR-143 expression is associated with poor prognosis of patients with osteosarcoma underlying chemotherapy. The chemoresistance of osteosarcoma tumor cells to doxorubicin is associated with the downregulation of miR-143 expression, activation of ALDH1+CD133+ cells, activation of autophagy, and inhibition of cell death.
Key Molecule: hsa-mir-155 [46]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description During treatment with Dox or Cis in osteosarcoma cells, miR-155 expression was strongly induced. The increased miR-155 expression facilitated tumor cell proliferation via upregulating autophagy, thus, facilitated the resistance of osteosarcoma cells to Dox or Cis.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [9]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell colony Activation hsa05200
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
KHOS cells Bone Homo sapiens (Human) CVCL_2546
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Colony formation assay
Mechanism Description CircPVT1 knockdown reduces the expression of classical multidrug resistance related gene-ABCB1 in OS cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Syndecan-2 (SDC2) [37]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
Experiment for
Molecule Alteration
Luciferase reporter assay; Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description miR20a-5p modulates multi-drug resistance by repressing SDC2 expression in OS cells.
Key Molecule: Nucleosome-binding protein 1 (NSBP1) [40]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell autophagy Activation hsa04140
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
hFOB1.19 cells Fetal bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Luciferase activity assay; Western blot analysis
Experiment for
Drug Resistance
IC50 assay; Flow cytometric analysis
Mechanism Description miR140-5p/HMGN5/autophagy regulatory loop plays a critical role in chemoresistance in osteosarcoma, miR 140-5p regulates osteosarcoma chemoresistance by targeting HMGN5 and autophagy.
Key Molecule: Forkhead box protein C2 (FOXC2) [41]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Colony formation assay
Mechanism Description Antisense LncRNA FOXC2-AS1 promotes doxorubicin resistance in osteosarcoma by increasing the expression of FOXC2. FOXC2-AS1 contributes to doxorubicin resistance by increasing FOXC2 and further facilitating ABCB1.
Key Molecule: Type-1 angiotensin II receptor (AGTR1) [2]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Annexin V-FITC/propidium iodide (PI) staining assay
Mechanism Description The miR34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene.
Key Molecule: Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) [42]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description The up-regulation of MCL1 reversed the sensitivity of doxorubicin induced by miR-320a mimics and knockdown of SNHG12.
Key Molecule: Adenylate kinase 4 (AK4) [3]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Activation hsa05200
NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis; RIP assay; Luciferase reporter assay
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description The Ak4 gene is one of the targets of miR-199a-3p and negatively correlates with the effect of miR-199a-3p on OS drug-resistance.
Key Molecule: Bcl-2-like protein 11 (BCL2L11) [43]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/BCL2 signaling pathway Regulation hsa04933
Cell apoptosis Activation hsa04210
NF-kappaB signaling pathway Regulation hsa04064
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description microRNA-184 modulates doxorubicin resistance in osteosarcoma cells by targeting BCL2L1 and enhancing the level of it.
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
Key Molecule: Beclin-1 (BECN1) [44]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description Down-regulation of miR-30a contributed to chemoresistance of osteosarcoma cells through regulating autophagy. Furthermore, to investigate the mechanism of miR-130a in regulating autophagy, bioinformatics analysis was performed. The results showed that the 3'-UTR region of Beclin-1 were the binding sites for miR-30a. Consistently, previous studies demonstrated that Beclin-1 was the directly target of miR-30a.
Key Molecule: E3 ubiquitin-protein ligase ZNRF3 (ZNRF3) [11]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
Wnt/Beta-catenin signaling pathway Regulation hsa04310
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
hFOB1.19 cells Fetal bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-146b-5p was highly expressed in human osteosarcoma tissues and an elevated expression of miR-146b-5p was observed in human osteosarcoma tissues after chemotherapy. Furthermore, it was shown that miR-146b-5p overexpression promoted migration and invasiveness. miR-146b-5p overexpression also increased resistance to chemotherapy. Moreover, knockdown of miR-146b-5p substantially inhibited migration and invasion of osteosarcoma cells as well as rendered them significantly more sensitive to chemotherapy. Results of western blot assay indicated that miR-146b-5p increased MMP-16 protein expression and showed a decrease of ZNRF3 protein. Whereas, IWR-1-endo, an inhibitor of Wnt/beta-catenin, suppressed the decrease in apoptosis of osteosarcoma cells caused by miR-146b-5p overexpression. These results indicated that miR-146b-5p promoted proliferation, migration and invasiveness.
Key Molecule: Autophagy-related protein 2 homolog B (ATG2B) [45]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Matrigel colony formation assay; Hoechst33342 staining assay
Mechanism Description In chemoresistant SAOS-2 and U2OS osteosarcomas cells, miR-143 levels were significantly downregulated and accompanied by increases in ATG2B, Bcl-2, and/or LC3-II protein levels, high rate of ALDH1+CD133+ cells, and an increase in Matrigel colony formation ability. H2O2 upregulated p53 and miR-143, but downregulated ATG2B, Bcl-2, and LC3-I expression in U2OS cells (wild-type p53) but not in SAOS-2 (p53-null) cells. Forced miR-143 expression significantly reversed chemoresistance as well as downregulation of ATG2B, LC3-I, and Bcl-2 expression in SAOS-2- and U2OS-resistant cells. Forced miR-143 expression significantly inhibited tumor growth in xenograft SAOS-2-Dox and U2OS-Dox animal models. Loss of miR-143 expression is associated with poor prognosis of patients with osteosarcoma underlying chemotherapy. The chemoresistance of osteosarcoma tumor cells to doxorubicin is associated with the downregulation of miR-143 expression, activation of ALDH1+CD133+ cells, activation of autophagy, and inhibition of cell death.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [45]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Matrigel colony formation assay; Hoechst33342 staining assay
Mechanism Description In chemoresistant SAOS-2 and U2OS osteosarcomas cells, miR-143 levels were significantly downregulated and accompanied by increases in ATG2B, Bcl-2, and/or LC3-II protein levels, high rate of ALDH1+CD133+ cells, and an increase in Matrigel colony formation ability. H2O2 upregulated p53 and miR-143, but downregulated ATG2B, Bcl-2, and LC3-I expression in U2OS cells (wild-type p53) but not in SAOS-2 (p53-null) cells. Forced miR-143 expression significantly reversed chemoresistance as well as downregulation of ATG2B, LC3-I, and Bcl-2 expression in SAOS-2- and U2OS-resistant cells. Forced miR-143 expression significantly inhibited tumor growth in xenograft SAOS-2-Dox and U2OS-Dox animal models. Loss of miR-143 expression is associated with poor prognosis of patients with osteosarcoma underlying chemotherapy. The chemoresistance of osteosarcoma tumor cells to doxorubicin is associated with the downregulation of miR-143 expression, activation of ALDH1+CD133+ cells, activation of autophagy, and inhibition of cell death.
Key Molecule: Microtubule-associated proteins 1A/1B light chain 3A (MAP1LC3A) [45]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Matrigel colony formation assay; Hoechst33342 staining assay
Mechanism Description In chemoresistant SAOS-2 and U2OS osteosarcomas cells, miR-143 levels were significantly downregulated and accompanied by increases in ATG2B, Bcl-2, and/or LC3-II protein levels, high rate of ALDH1+CD133+ cells, and an increase in Matrigel colony formation ability. H2O2 upregulated p53 and miR-143, but downregulated ATG2B, Bcl-2, and LC3-I expression in U2OS cells (wild-type p53) but not in SAOS-2 (p53-null) cells. Forced miR-143 expression significantly reversed chemoresistance as well as downregulation of ATG2B, LC3-I, and Bcl-2 expression in SAOS-2- and U2OS-resistant cells. Forced miR-143 expression significantly inhibited tumor growth in xenograft SAOS-2-Dox and U2OS-Dox animal models. Loss of miR-143 expression is associated with poor prognosis of patients with osteosarcoma underlying chemotherapy. The chemoresistance of osteosarcoma tumor cells to doxorubicin is associated with the downregulation of miR-143 expression, activation of ALDH1+CD133+ cells, activation of autophagy, and inhibition of cell death.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: FOXF1 adjacent non-coding developmental regulatory RNA (FENDRR) [47]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qPCR; Microarray assay
Experiment for
Drug Resistance
CCK8 assay; Flow cytometric analysis
Mechanism Description LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through down-regulating ABCB1 and ABCC1.
Key Molecule: hsa-mir-100 [48]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell growth Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
MTT assay; CCK8 assay
Mechanism Description Either ZNRF2 overexpression or miR100 depletion increased in vitro OS cell growth and improved cell survival at the presence of Doxorubicin. miR100 bindS to the 3'-UTR of ZNRF2 mRNA to prevent its protein translation, re-expression of miR100 may inhibit OS cell growth and decrease OS cell chemo-resistance.
Key Molecule: Phosphate cytidylyltransferase 1A, choline (PCYT1A) [49]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
TUNEL Assay; MTT assay; Flow cytometric analysis
Mechanism Description LncRNA CTA-miR210 axis plays an important role in reducing OS chemoresistance. LncRNA CTA could be activated by doxorubicin (DOX), and could promote OS cell apoptosis by competitively binding miR210, while inhibit cell autophagy.
Key Molecule: hsa-mir-210 [49]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR; Dual luciferase reporter assay
Experiment for
Drug Resistance
TUNEL Assay; MTT assay; Flow cytometric analysis
Mechanism Description LncRNA CTA-miR210 axis plays an important role in reducing OS chemoresistance. LncRNA CTA could be activated by doxorubicin (DOX), and could promote OS cell apoptosis by competitively binding miR210, while inhibit cell autophagy.
Key Molecule: hsa-mir-410 [20]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description microRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma, miR410 directly decreased ATG16L1 expression by targeting its 3'-untranslated region.
Key Molecule: hsa-mir-124 [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: hsa-miR-199a-3p [51]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
KHOS cells Bone Homo sapiens (Human) CVCL_2546
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description CD44 was overexpressed in metastatic and recurrent osteosarcoma as compared with primary tumors. Higher expression of CD44 was found in both patients with shorter survival and patients who exhibited unfavorable response to chemotherapy before surgical resection. Additionally, the 3'-untranslated region of CD44 mRNA was the direct target of microRNA-199a-3p (miR-199a-3p). Overexpression of miR-199a-3p significantly inhibited CD44 expression in osteosarcoma cells. miR-199a-3p is One of the most dramatically decreased miRs in osteosarcoma cells and tumor tissues as compared with normal osteoblast cells. Transfection of miR-199a-3p significantly increased the drug sensitivity through down-regulation of CD44 in osteosarcoma cells. Taken together, these results suggest that the CD44-miR-199a-3p axis plays an important role in the development of metastasis, recurrence, and drug resistance of osteosarcoma. Developing strategies to target CD44 may improve the clinical outcome of osteosarcoma.
Key Molecule: hsa-mir-382 [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: hsa-mir-101 [52]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Quantitative GFP-LC3 analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The miR-101 not only decreases the formation of autophagic vesicles but also reduces the expression of LC-3II and Atg 4. This part of the study shows that miR-101 blocks chemotherapy-induced autophagy in OS cells. The sensitivity of OS cells to chemotherapy is increased by miR-101 blocked autophagy. miR-101 blocked the chemotherapy induced autophagy, and the blocked autophagy by miR-101 enhances the sensitivity of the OS cell line U-2 in vitro.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [47]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Flow cytometric analysis
Mechanism Description LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through down-regulating ABCB1 and ABCC1.
Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [47]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
HOS cells Bone Homo sapiens (Human) CVCL_0312
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Flow cytometric analysis
Mechanism Description LncRNA FENDRR sensitizes doxorubicin-resistance of osteosarcoma cells through down-regulating ABCB1 and ABCC1.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: E3 ubiquitin-protein ligase ZNRF2 (ZNRF2) [48]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell growth Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blot analysis; Luciferase reporter assay
Experiment for
Drug Resistance
MTT assay; CCK8 assay
Mechanism Description Either ZNRF2 overexpression or miR100 depletion increased in vitro OS cell growth and improved cell survival at the presence of Doxorubicin. miR100 bindS to the 3'-UTR of ZNRF2 mRNA to prevent its protein translation, re-expression of miR100 may inhibit OS cell growth and decrease OS cell chemo-resistance.
Key Molecule: Autophagy-related protein 16-1 (ATG16L1) [20]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
Luciferase reporter assay; Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description microRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma, miR410 directly decreased ATG16L1 expression by targeting its 3'-untranslated region.
Key Molecule: ATM interactor (ATMIN) [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1) [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: Extracellular matrix receptor III (CD44) [51]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
KHOS cells Bone Homo sapiens (Human) CVCL_2546
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description CD44 was overexpressed in metastatic and recurrent osteosarcoma as compared with primary tumors. Higher expression of CD44 was found in both patients with shorter survival and patients who exhibited unfavorable response to chemotherapy before surgical resection. Additionally, the 3'-untranslated region of CD44 mRNA was the direct target of microRNA-199a-3p (miR-199a-3p). Overexpression of miR-199a-3p significantly inhibited CD44 expression in osteosarcoma cells. miR-199a-3p is One of the most dramatically decreased miRs in osteosarcoma cells and tumor tissues as compared with normal osteoblast cells. Transfection of miR-199a-3p significantly increased the drug sensitivity through down-regulation of CD44 in osteosarcoma cells. Taken together, these results suggest that the CD44-miR-199a-3p axis plays an important role in the development of metastasis, recurrence, and drug resistance of osteosarcoma. Developing strategies to target CD44 may improve the clinical outcome of osteosarcoma.
Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: Krueppel-like factor 12 (KLF12) [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: Ubiquitin-like modifier-activating enzyme Atg 4 (ATG4) [52]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The miR-101 not only decreases the formation of autophagic vesicles but also reduces the expression of LC-3II and Atg 4. This part of the study shows that miR-101 blocks chemotherapy-induced autophagy in OS cells. The sensitivity of OS cells to chemotherapy is increased by miR-101 blocked autophagy. miR-101 blocked the chemotherapy induced autophagy, and the blocked autophagy by miR-101 enhances the sensitivity of the OS cell line U-2 in vitro.
Key Molecule: Microtubule-associated protein 1 light chain3 (LC3) [52]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Doxorubicin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The miR-101 not only decreases the formation of autophagic vesicles but also reduces the expression of LC-3II and Atg 4. This part of the study shows that miR-101 blocks chemotherapy-induced autophagy in OS cells. The sensitivity of OS cells to chemotherapy is increased by miR-101 blocked autophagy. miR-101 blocked the chemotherapy induced autophagy, and the blocked autophagy by miR-101 enhances the sensitivity of the OS cell line U-2 in vitro.
Etoposide
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-34a-5p [2], [6]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ATF2/ATF3/ATF4 signaling pathway Inhibition hsa04915
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Annexin V-FITC/propidium iodide (PI) staining assay
Mechanism Description The miR34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene. And miR34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene.
Key Molecule: hsa-miR-20a-5p [37]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description miR20a-5p modulates multi-drug resistance by repressing SDC2 expression in OS cells.
Key Molecule: Delta-like protein 1 (DLL1) [6]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ATF2/ATF3/ATF4 signaling pathway Inhibition hsa04915
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
IC50 assay; Flow cytometric analysis
Mechanism Description miR34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene. The activity of the ATF2/ATF3/ATF4 pathway was reduced in the miR34a-5p mimic-transfected G-292 cells but increased in the miR34a-5p antagomiRtransfected SJSA-1 cells, hence the ATF2/ATF3/ATF4 pathway was validated to be involved in the OS chemoresistance mediated by miR34a-5p.
Key Molecule: hsa-miR-34a-5p [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Syndecan-2 (SDC2) [37]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
Experiment for
Molecule Alteration
Luciferase reporter assay; Western blot analysis
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description miR20a-5p modulates multi-drug resistance by repressing SDC2 expression in OS cells.
Key Molecule: Type-1 angiotensin II receptor (AGTR1) [2]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Annexin V-FITC/propidium iodide (PI) staining assay
Mechanism Description The miR34a-5p promotes the multi-chemoresistance of osteosarcoma via repression of the AGTR1 gene.
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-124 [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: hsa-mir-103 [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: hsa-miR-107 [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: ATM interactor (ATMIN) [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1) [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: E2F1-regulated inhibitor of cell death (ERICD) [53]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Fluorescence-activated cell sorting analysis
Mechanism Description The long non-coding RNA ERIC is regulated by E2F and modulates the cellular response to DNA damage, ERIC levels were increased following DNA damage by the chemotherapeutic drug Etoposide, and inhibition of ERIC expression enhanced Etoposide -induced apoptosis.
Key Molecule: DNA repair protein RAD51 homolog 1 (RAD51) [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: DNA repair protein RAD51 homolog 4 (RAD51D) [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Etoposide
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Fluorouracil
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-140 [54]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Fluorouracil
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-140 is involved in the chemoresistance by reduced cell proliferation via G1 and G2 phase arrest mediated in part.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Histone deacetylase 4 (HDAC4) [54]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Fluorouracil
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis; Immunofluorescence analysis
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-140 is involved in the chemoresistance by reduced cell proliferation via G1 and G2 phase arrest mediated in part.
Gemcitabine
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-152 [36]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Gemcitabine
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
c-Met/PI3K/AKT signaling pathway Activation hsa01521
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay; Soft agar assay
Mechanism Description LncRNAPVT1 targets miR-152 to enhance chemoresistance of osteosarcoma to gemcitabine through activating c-MET/PI3k/AkT pathway.
Key Molecule: Pvt1 oncogene (PVT1) [36]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Gemcitabine
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
c-Met/PI3K/AKT signaling pathway Activation hsa01521
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay; Soft agar assay
Mechanism Description LncRNAPVT1 targets miR-152 to enhance chemoresistance of osteosarcoma to gemcitabine through activating c-MET/PI3k/AkT pathway.
Ifosfamide
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Tripartite motif containing 37 (TRIM37) [55]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Ifosfamide
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Wnt/Beta-catenin signaling pathway Activation hsa04310
In Vitro Model Saccharomyces cerevisiae strain BY4742 4932
SH-1-V6 cells Esophagus Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration
qRT-PCR
Mechanism Description High expression of TRIM37 mRNA and protein was observed in paediatric osteosarcoma tumour samples. Treatment of cell lines Saos-2 and MG-63 with ifosfamide, doxorubicin, cisplatin, or methotrexate induced TRIM37 expression. Upregulation of TRIM37 in vitro induced drug resistance, whereas TRIM37 knockdown restored chemosensitivity. The TRIM37-induced chemoresistance was found to be partially dependent on the activation of the Wnt/beta-catenin signalling pathway.
Lobaplatin
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Far upstream element-binding protein 1 (FUBP1) [56]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Lobaplatin
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model PC-3 cells Prostate Homo sapiens (Human) CVCL_0035
SH-1-V6 cells Esophagus Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
CCK8 assay
Mechanism Description FUBP1 knockdown conferred lobaplatin sensitivity of osteosarcoma SaOS-2 Cells.
Methotrexate
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Lung cancer associated transcript 1 (LUCAT1) [57]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell proliferation Activation hsa05200
LUCAT1/miR200c/ABCB1 pathway Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
HFOB cells Bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
CCK8 assay; Transwell invasion assay
Mechanism Description The modulation of LUCAT1 on ABCB1 through sponging miR200c. LncRNA LUCAT1 knockdown suppress the expression levels drug resistance related genes, proliferation, invasion and tumor growth of osteosarcoma cells in vitro and vivo, hence, LUCAT1 upregulation leads to improved chemoresistance.
Key Molecule: hsa-mir-200c [57]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell proliferation Activation hsa05200
LUCAT1/miR200c/ABCB1 pathway Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
HFOB cells Bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Transwell invasion assay
Mechanism Description Long non-coding RNA LUCAT1 modulates methotrexate resistance in osteosarcoma via miR200c/ABCB1 axis.
Key Molecule: hsa-mir-375 [38]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
In Vivo Model A retrospective survey in conducting clinical studies Homo sapiens
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Multivariate analysis of overall survival or disease-free survival assay
Mechanism Description miR375 overexpression could increase the cisplatin sensitivity of human gastric cancer cells by regulating ERBB2.
Key Molecule: Delta-like protein 1 (DLL1) [6]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ATF2/ATF3/ATF4 signaling pathway Inhibition hsa04915
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
IC50 assay; Flow cytometric analysis
Mechanism Description miR34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene. The activity of the ATF2/ATF3/ATF4 pathway was reduced in the miR34a-5p mimic-transfected G-292 cells but increased in the miR34a-5p antagomiRtransfected SJSA-1 cells, hence the ATF2/ATF3/ATF4 pathway was validated to be involved in the OS chemoresistance mediated by miR34a-5p.
Key Molecule: hsa-miR-34a-5p [6]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation ATF2/ATF3/ATF4 signaling pathway Inhibition hsa04915
In Vitro Model G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
IC50 assay; Flow cytometric analysis
Mechanism Description miR34a-5p promotes multi-chemoresistance of osteosarcoma through down-regulation of the DLL1 gene. The activity of the ATF2/ATF3/ATF4 pathway was reduced in the miR34a-5p mimic-transfected G-292 cells but increased in the miR34a-5p antagomiRtransfected SJSA-1 cells, hence the ATF2/ATF3/ATF4 pathway was validated to be involved in the OS chemoresistance mediated by miR34a-5p.
Key Molecule: hsa-miR-34a-5p [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
Key Molecule: hsa-miR-146b-5p [11]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
Wnt/Beta-catenin signaling pathway Regulation hsa04310
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
hFOB1.19 cells Fetal bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-146b-5p was highly expressed in human osteosarcoma tissues and an elevated expression of miR-146b-5p was observed in human osteosarcoma tissues after chemotherapy. Furthermore, it was shown that miR-146b-5p overexpression promoted migration and invasiveness. miR-146b-5p overexpression also increased resistance to chemotherapy. Moreover, knockdown of miR-146b-5p substantially inhibited migration and invasion of osteosarcoma cells as well as rendered them significantly more sensitive to chemotherapy. Results of western blot assay indicated that miR-146b-5p increased MMP-16 protein expression and showed a decrease of ZNRF3 protein. Whereas, IWR-1-endo, an inhibitor of Wnt/beta-catenin, suppressed the decrease in apoptosis of osteosarcoma cells caused by miR-146b-5p overexpression. These results indicated that miR-146b-5p promoted proliferation, migration and invasiveness.
Key Molecule: hsa-mir-215 [58]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
p53 signaling pathway Activation hsa04115
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-215, through the suppression of DTL expression, induces a decreased cell proliferation by causing G2-arrest, thereby leading to an increase in chemoresistance to MTX and TDX.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [57]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell colony Activation hsa05200
Cell senescence Inhibition hsa04218
Cell viability Activation hsa05200
LUCAT1/miR200c/ABCB1 pathway Regulation hsa05206
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HOS cells Bone Homo sapiens (Human) CVCL_0312
HFOB cells Bone Homo sapiens (Human) CVCL_3708
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis; Luciferase reporter assay
Experiment for
Drug Resistance
CCK8 assay; Transwell invasion assay
Mechanism Description LncRNA LUCAT1 and ABCB1 protein were both up-regulated in MG63/MTX and HOS/MTX cells when treated with methotrexate. ABCB1, acting as a vital protein of drug resistance, participated in the multiple drug resistance occurrence.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [4]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
MEF2 signaling pathway Regulation hsa04013
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
G-292 cells Bone Homo sapiens (Human) CVCL_2909
SJSA-1 cells Bone Homo sapiens (Human) CVCL_1697
MG63.2 cells Bone Homo sapiens (Human) CVCL_R705
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description The down-regulation of CD117 mediated by miR-34a-5p might be one of the reasons for OS drug resistance. CD117 may also regulate other processes, including cell adhesion, differentiation and migration, which are significant for cancer development and treatment.
Key Molecule: E3 ubiquitin-protein ligase ZNRF3 (ZNRF3) [11]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
Cell migration Activation hsa04670
Cell proliferation Activation hsa05200
Wnt/Beta-catenin signaling pathway Regulation hsa04310
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
hFOB1.19 cells Fetal bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description miR-146b-5p was highly expressed in human osteosarcoma tissues and an elevated expression of miR-146b-5p was observed in human osteosarcoma tissues after chemotherapy. Furthermore, it was shown that miR-146b-5p overexpression promoted migration and invasiveness. miR-146b-5p overexpression also increased resistance to chemotherapy. Moreover, knockdown of miR-146b-5p substantially inhibited migration and invasion of osteosarcoma cells as well as rendered them significantly more sensitive to chemotherapy. Results of western blot assay indicated that miR-146b-5p increased MMP-16 protein expression and showed a decrease of ZNRF3 protein. Whereas, IWR-1-endo, an inhibitor of Wnt/beta-catenin, suppressed the decrease in apoptosis of osteosarcoma cells caused by miR-146b-5p overexpression. These results indicated that miR-146b-5p promoted proliferation, migration and invasiveness.
Key Molecule: Dihydrofolate reductase (DHFR) [58]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
p53 signaling pathway Activation hsa04115
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis; Immunofluorescence analysis
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-215, through the suppression of DTL expression, induces a decreased cell proliferation by causing G2-arrest, thereby leading to an increase in chemoresistance to MTX and TDX.
Key Molecule: Thymidylate synthase (TYMS) [58]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
p53 signaling pathway Activation hsa04115
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis; Immunofluorescence analysis
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-215, through the suppression of DTL expression, induces a decreased cell proliferation by causing G2-arrest, thereby leading to an increase in chemoresistance to MTX and TDX.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-29a [59]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description Overexpression of miR-29a suppressed MTX resistance and promoted cell apoptosis by downregulating MCL1 expression.
Key Molecule: hsa-mir-29b [59]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description Overexpression of miR-29b suppressed MTX resistance and promoted cell apoptosis by downregulating MCL1 expression.
Key Molecule: hsa-mir-29c [59]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description Overexpression of miR-29c suppressed MTX resistance and promoted cell apoptosis by downregulating MCL1 expression.
Key Molecule: hsa-mir-382 [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: hsa-mir-140 [54]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-140 is involved in the chemoresistance by reduced cell proliferation via G1 and G2 phase arrest mediated in part.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Collagen alpha-1(III) chain (COL3A1) [59]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blot analysis; RT-qPCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description Overexpression of miR-29a suppressed MTX resistance and promoted cell apoptosis by downregulating COL3A1 expression.
Key Molecule: Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) [59]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Methotrexate
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blot analysis; RT-qPCR
Experiment for
Drug Resistance
CCK8 assay; Flow cytometry assay
Mechanism Description Overexpression of miR-29a suppressed MTX resistance and promoted cell apoptosis by downregulating MCL1 expression.
Key Molecule: Homeodomain-interacting protein kinase 3 (HIPK3) [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: Krueppel-like factor 12 (KLF12) [31]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
MNNG/HOS cells Bone Homo sapiens (Human) CVCL_0439
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description Decreased miR-382 was associated with poor survival in OS patients. Overexpression of miR-382 inhibited cell growth and chemoresistance by targeting kLF12 and HIPk3, respectively. In contrast, inhibition of miR-382 or overexpression of target genes stimulated OS cell growth and chemoresistance both in vitro and in vivo.
Key Molecule: Histone deacetylase 4 (HDAC4) [54]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Methotrexate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis; Immunofluorescence analysis
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-140 is involved in the chemoresistance by reduced cell proliferation via G1 and G2 phase arrest mediated in part.
Oxycodone
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Cytochrome P450 family 3 subfamily A (CYP3A) [60]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Oxycodone
Experimental Note Identified from the Human Clinical Data
Mechanism Description Oxycodone is a semisynthetic opioid receptor agonist, and is frequently used for pain control in patients with cancer. Most oxycodone is metabolized by N-demethylation to noroxycodone by CYP3A. Rifampin is a strong inducer of several drug-metabolizing enzymes, including CYP3A. Hence, rifampin-induced CYP3A activity may decrease the effect of oxycodone.
Paclitaxel
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Mitosis associated long intergenic non-coding RNA 1 (MALINC1) [61]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Paclitaxel
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Silencing of MA-linc1 in unsynchronized cells results in fewer cells in G1 and a concomitant increase in the number of cells in all other stages of the cell cycle, particularly in G2/M. Moreover, its silencing in M phase-arrested cells inhibits mitosis exit. The effect of MA-linc1 on cell cycle progression is mediated, at least in part, by repression of its neighboring gene, Puralpha, a cell cycle regulator whose expression induces cell cycle arrest. Importantly, high levels of MA-linc1 are correlated with decreased survival of breast and lung cancer patients and its silencing sensitizes cancer cells to the apoptotic effect of the M phase specific chemotherapeutic drug, Paclitaxel. This enhancement of Paclitaxel-induced apoptosis is also Puralpha-related.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Transcriptional activator protein Pur-alpha (PURA) [61]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Paclitaxel
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Silencing of MA-linc1 in unsynchronized cells results in fewer cells in G1 and a concomitant increase in the number of cells in all other stages of the cell cycle, particularly in G2/M. Moreover, its silencing in M phase-arrested cells inhibits mitosis exit. The effect of MA-linc1 on cell cycle progression is mediated, at least in part, by repression of its neighboring gene, Puralpha, a cell cycle regulator whose expression induces cell cycle arrest. Importantly, high levels of MA-linc1 are correlated with decreased survival of breast and lung cancer patients and its silencing sensitizes cancer cells to the apoptotic effect of the M phase specific chemotherapeutic drug, Paclitaxel. This enhancement of Paclitaxel-induced apoptosis is also Puralpha-related.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-422a [22]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Paclitaxel
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFOB cells Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
MTT assay; Flow cytometric analysis of apoptosis; Transwell assay
Mechanism Description Overexpression of miR422a inhibits cell proliferation and invasion, and enhances chemosensitivity by directly targeting TGFbeta2 in osteosarcoma cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Transforming growth factor beta-2 proprotein (TGFB2) [22]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Paclitaxel
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
SAOS-2 cells Bone marrow Homo sapiens (Human) CVCL_0548
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFOB cells Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
Western blot analysis; Dual luciferase activity assay
Experiment for
Drug Resistance
MTT assay; Flow cytometric analysis of apoptosis; Transwell assay
Mechanism Description Overexpression of miR422a inhibits cell proliferation and invasion, and enhances chemosensitivity by directly targeting TGFbeta2 in osteosarcoma cells.
Raltitrexed
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-215 [58]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Resistant Drug Raltitrexed
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
p53 signaling pathway Activation hsa04115
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-215, through the suppression of DTL expression, induces a decreased cell proliferation by causing G2-arrest, thereby leading to an increase in chemoresistance to MTX and TDX.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Dihydrofolate reductase (DHFR) [58]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Raltitrexed
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
p53 signaling pathway Activation hsa04115
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis; Immunofluorescence analysis
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-215, through the suppression of DTL expression, induces a decreased cell proliferation by causing G2-arrest, thereby leading to an increase in chemoresistance to MTX and TDX.
Key Molecule: Thymidylate synthase (TYMS) [58]
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Resistant Drug Raltitrexed
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
p53 signaling pathway Activation hsa04115
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis; Immunofluorescence analysis
Experiment for
Drug Resistance
WST-1 assay
Mechanism Description miR-215, through the suppression of DTL expression, induces a decreased cell proliferation by causing G2-arrest, thereby leading to an increase in chemoresistance to MTX and TDX.
Silibinin
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-494 [62]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Silibinin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
qPCR
Experiment for
Drug Resistance
TUNEL cell apoptosis assay; XTT cell proliferation assay; MTT cell proliferation assay; Colony formation assay
Mechanism Description MMP-9 was targeted and negatively regulated by hsa-miR494 which inhibited cell proliferation and induced cell apoptosis. Silybin inhibited OS cell viability by altering the protein levels of beta-catenin and RUNX2, thus upregulating the level of hsa-miR494.
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: Matrix metalloproteinase-9 (MMP9) [62]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Silibinin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
Experiment for
Molecule Alteration
qPCR; Western blot analysis
Experiment for
Drug Resistance
TUNEL cell apoptosis assay; XTT cell proliferation assay; MTT cell proliferation assay; Colony formation assay
Mechanism Description MMP-9 was targeted and negatively regulated by hsa-miR494 which inhibited cell proliferation and induced cell apoptosis. Silybin inhibited OS cell viability by altering the protein levels of beta-catenin and RUNX2, thus upregulating the level of hsa-miR494.
Sirolimus
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-410 [20]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Sirolimus
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description microRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma, miR410 directly decreased ATG16L1 expression by targeting its 3'-untranslated region.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Autophagy-related protein 16-1 (ATG16L1) [20]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Sirolimus
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
HFob 1.19 Bone Homo sapiens (Human) CVCL_3708
Experiment for
Molecule Alteration
Luciferase reporter assay; Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description microRNA-410 regulates autophagy-related gene ATG16L1 expression and enhances chemosensitivity via autophagy inhibition in osteosarcoma, miR410 directly decreased ATG16L1 expression by targeting its 3'-untranslated region.
Epigallocatechin gallate
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-126 [63]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Epigallocatechin gallate
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model MG63 cells Bone marrow Homo sapiens (Human) CVCL_0426
U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Flow cytometry assay
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description Overexpression of miR-126 sensitizes osteosarcoma cells to apoptosis induced by epigallocatechin-3-gallate.
Clinical Trial Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Camptothecin
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-124 [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Camptothecin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: hsa-mir-103 [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Camptothecin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: hsa-miR-107 [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Camptothecin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: ATM interactor (ATMIN) [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Camptothecin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1) [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Camptothecin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: DNA repair protein RAD51 homolog 1 (RAD51) [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Camptothecin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Key Molecule: DNA repair protein RAD51 homolog 4 (RAD51D) [33]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Camptothecin
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model U2OS cells Bone Homo sapiens (Human) CVCL_0042
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Survival assay/crystal violet staining assay
Mechanism Description miR-103 and miR-107 reduced homology-directed repair and sensitized cells to various DNA damaging agents, including cisplatin and a PARP inhibitor. Mechanistic analyses revealed that both miR-103 and miR-107 directly target and regulate RAD51 and RAD51D, which is critical for miR-103/107-mediated chemosensitization.
Preclinical Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
MRK-003
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.A1552G (c.4655C>G)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.A1552V (c.4655C>T)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.E1567K (c.4699G>A)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.A1570G (c.4709C>G)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.V1575A (c.4724T>C)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.V1599M (c.4795G>A)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.V1676I (c.5026G>A)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.I1680S (c.5039T>G)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.R1683W (c.5047C>T)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Key Molecule: Neurogenic locus notch homolog protein 1 (NOTCH1) [64]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Missense mutation
p.A1707T (c.5119G>A)
Sensitive Drug MRK-003
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MDA-MB-157 cells Breast Homo sapiens (Human) CVCL_0618
TNsBC cells Breast Homo sapiens (Human) N.A.
T-ALL cells Bone marrow Homo sapiens (Human) CVCL_1736
HCC2218 cells Breast Homo sapiens (Human) CVCL_1263
HCC1187 cells Breast Homo sapiens (Human) CVCL_1247
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
Cell Titer-Glo luminescent assay; Luciferase assay
Investigative Drug(s)
1 drug(s) in total
Click to Show/Hide the Full List of Drugs
Iridium
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-124 [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Up-regulation
Sensitive Drug Iridium
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
Experiment for
Molecule Alteration
RT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: ATM interactor (ATMIN) [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Iridium
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1) [50]
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
Molecule Alteration Expression
Down-regulation
Sensitive Drug Iridium
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
T47D cells Breast Homo sapiens (Human) CVCL_0553
ZR75-1 cells Breast Homo sapiens (Human) CVCL_0588
HCC1937 cells Breast Homo sapiens (Human) CVCL_0290
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-124 may be involved in DNA repair by directly targeting ATMIN and PARP1, suggesting that multiple DNA repair pathways are affected by miR-124 and therefore manipulation of miR-124 level/activity may improve the efficacy of chemotherapies that induce DNA damage. repression of ATMIN (+) the HR repair defect induced by miR-124, and restoration of ATMIN reversed the effect of miR-124 overexpression in breast cancer cells. Therefore, it is intriguing to further speculate which of the multiple roles of ATMIN is specifically affected in breast carcinogenesis. On the other hand, PARP1-mediated processes play a role in oncogenesis, cancer progression, and therapeutic resistance.
References
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