Drug Information

Drug (ID: DG00148) and It's Reported Resistant Information
Name
Etoposide
Synonyms
Etoposide; 33419-42-0; VePesid; Toposar; trans-Etoposide; Lastet; (-)-Etoposide; Zuyeyidal; Etoposidum; Etoposido; Vepesid J; Eposin; Etoposidum [INN-Latin]; Etoposide (VP16); VP 16-213; VP 16 (pharmaceutical); Etoposido [INN-Spanish]; Etopophos (phosphate salt); VP-16-213; 4-Demethylepipodophyllotoxin beta-D-ethylideneglucoside; VP 16213; UNII-6PLQ3CP4P3; NK 171; NSC 141540; CCRIS 2392; HSDB 6517; 4'-Demethylepipodophyllotoxin 9-(4,6-O-(R)-ethylidene-beta-D-glucopyranoside); EINECS 251-509-1; NSC-141540; Eposide; Etopol; Etosid; Vepeside; Demethyl EpipodophyllotoxinEthylidine Glucoside; E0675; Demethyl-epiodophyllotoxin ethylidene glucoside; Epipodophyllotoxin VP-16213; Eposin (TN); Etopophos (TN); Trans-Etoposide; VePESID (TN); Vepesid (TN); DEMETHY-EPIPODOPHYLLOTOXIN, ETHYLIDENE GLUCOSIDE; VP-16 (TN); Demethylepipodophyllotoxin-beta-D-ethylideneglucoside; Etoposide (JP15/USP/INN); Etoposide [USAN:INN:BAN:JAN]; Eposin, Vepesid, VP-16, Toposar, Etoposide; Epipodophyllotoxin, 4'-demethyl-, 4,6-O-ethylidene-beta-D-glucopyranoside; Epipodophyllotoxin, 4'-demethyl-, 4,6-O-ethylidene-beta-D-glucopyranoside (8CI); Epipodophyllotoxin, 4'-demethyl-, 9-(4,6-O-ethylidene-beta-D-glucopyranoside); 4'-Demethyl-epipodophyllotoxin 9-[4,6-O-(R)-ethylidene-beta-D-glucopyranoside; 4'-Demethylepipodophyllotoxin 9-(4,6-O-ethylidene-beta-D-glucopyranoside); 4'-Demethylepipodophyllotoxin ethylidene-beta-D-glucoside; 4'-O-Demethyl-1-O-(4,6-O-ethylidene-beta-D-glucopyranosyl)epipodophyllotoxin; 4-Demethylepipodophyllotoxin-beta-D-ethylideneglucoside
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Indication
In total 1 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (10 diseases)
Brain cancer [ICD-11: 2A00]
[2]
Breast cancer [ICD-11: 2C60]
[3]
Ewing sarcoma [ICD-11: 2B52]
[2]
Head and neck cancer [ICD-11: 2D42]
[4]
Keloid/hypertrophic scars [ICD-11: EE60]
[5]
Lung cancer [ICD-11: 2C25]
[6]
Merkel cell carcinoma [ICD-11: 2C34]
[7]
Peripheral nerve sheath tumor [ICD-11: 2F3Y]
[8]
Peritoneal cancer [ICD-11: 2C51]
[9]
Pituitary cancer [ICD-11: 2F37]
[10]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (7 diseases)
Brain cancer [ICD-11: 2A00]
[11]
Breast cancer [ICD-11: 2C60]
[12]
Colon cancer [ICD-11: 2B90]
[13]
Lung cancer [ICD-11: 2C25]
[14]
Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]
[15]
Melanoma [ICD-11: 2C30]
[13]
Osteosarcoma [ICD-11: 2B51]
[16]
Target DNA topoisomerase II (TOP2) TOP2A_HUMAN ;
TOP2B_HUMAN 		[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C29H32O13
IsoSMILES
C[C@@H]1OC[C@@H]2[C@@H](O1)[C@@H]([C@H]([C@@H](O2)O[C@H]3[C@H]4COC(=O)[C@@H]4[C@@H](C5=CC6=C(C=C35)OCO6)C7=CC(=C(C(=C7)OC)O)OC)O)O
InChI
1S/C29H32O13/c1-11-36-9-20-27(40-11)24(31)25(32)29(41-20)42-26-14-7-17-16(38-10-39-17)6-13(14)21(22-15(26)8-37-28(22)33)12-4-18(34-2)23(30)19(5-12)35-3/h4-7,11,15,20-22,24-27,29-32H,8-10H2,1-3H3/t11-,15+,20-,21-,22+,24-,25-,26-,27-,29+/m1/s1
InChIKey
VJJPUSNTGOMMGY-MRVIYFEKSA-N
PubChem CID
36462
ChEBI ID
CHEBI:4911
TTD Drug ID
D0B7EB
VARIDT ID
DR00162
INTEDE ID
DR0669
DrugBank ID
DB00773
Type(s) of Resistant Mechanism of This Drug
  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 Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
Click to Show/Hide the Resistance Disease of This Class
Brain cancer [ICD-11: 2A00]
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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-125b [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Primitive neuroectodermal tumor [ICD-11: 2A00.08]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR125b-p53/BAKT signaling pathway Activation hsa05206
In Vitro Model RD-ES cells Bones Homo sapiens (Human) CVCL_2169
Sk-ES cells Bones Homo sapiens (Human) CVCL_0627
Sk-N-MC cells Bones Homo sapiens (Human) CVCL_0530
TC-71 cells Bones Homo sapiens (Human) CVCL_2213
VH-64 cells Bones Homo sapiens (Human) CVCL_9672
WE-68 cells Bones Homo sapiens (Human) CVCL_9717
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Celltiter-glo luminescent cell viability assay
Mechanism Description miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [11]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Ependymoma [ICD-11: 2A00.05]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Activation hsa04670
Cell invasion Activation hsa05200
In Vitro Model BXD-1425EPN cells Embryo Homo sapiens (Human) CVCL_Y105
EPN1 cells Embryo Homo sapiens (Human) N.A.
EPN7 cells Embryo Homo sapiens (Human) N.A.
EPN7R cells Embryo Homo sapiens (Human) N.A.
DKFZ-EP1 cells Embryo Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).
Key Molecule: Multidrug resistance protein 1 (ABCB1) [17]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Anaplastic astrocytoma [ICD-11: 2A00.04]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Malignant gliomas tissue N.A.
Experiment for
Molecule Alteration		 Immunohistochemistry assay
Experiment for
Drug Resistance		 Oncotech EDR assay
Mechanism Description Cisplatin and etoposide are both substrates for membrane-bound efflux pumps, such as MRP and MDR1, which prevent their entry into the extracellular space of the central nervous system. The low levels of in vitro drug resistance noted for cisplatin and etoposide may be explained in part by the absence of such a barrier in our in vitro assay system.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Bcl-2 homologous antagonist/killer (BAK1) [2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Primitive neuroectodermal tumor [ICD-11: 2A00.08]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR125b-p53/BAKT signaling pathway Activation hsa05206
In Vitro Model RD-ES cells Bones Homo sapiens (Human) CVCL_2169
Sk-ES cells Bones Homo sapiens (Human) CVCL_0627
Sk-N-MC cells Bones Homo sapiens (Human) CVCL_0530
TC-71 cells Bones Homo sapiens (Human) CVCL_2213
VH-64 cells Bones Homo sapiens (Human) CVCL_9672
WE-68 cells Bones Homo sapiens (Human) CVCL_9717
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Celltiter-glo luminescent cell viability assay
Mechanism Description miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-miR-296-3p [18]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Glioblastoma [ICD-11: 2A00.02]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model U251 cells Brain Homo sapiens (Human) CVCL_0021
U251AR cells Brain Homo sapiens (Human) CVCL_1G29
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description EAG1 channel might be involved in cell-cycle progression of tumour cells because a significant reduction in the proliferation of tumour cell lines could be achieved by inhibiting EAG1 expression using antisense oligonucleotides. Ectopic expression of miR-296-3p reduced EAG1 expression and suppressed cell proliferation drug resistance.
Key Molecule: hsa-mir-204 [19]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Neuroblastoma [ICD-11: 2A00.11]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model Kelly cells Adrenal Homo sapiens (Human) CVCL_2092
Sk-N-AS cells Adrenal Homo sapiens (Human) CVCL_1700
SH-SY5Y cells Abdomen Homo sapiens (Human) CVCL_0019
In Vivo Model Orthotopic xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-204 direct targeting of the 3' UTR of BCL2 and NTRk2 (TrkB). BCL2 has a critical role in ensuring the survival of early developing cell types, NTRk2 is also a well-established pro-survival oncogene in neuroblastoma, signalling the activation of the PI3k/AkT pathway, a significant mechanism of drug resistance in neuroblastoma. Ectopic miR-204 expression significantly increased sensitivity to cisplatin and etoposide in vitro.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [11]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Ependymoma [ICD-11: 2A00.05]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Activation hsa04670
Cell invasion Activation hsa05200
In Vitro Model BXD-1425EPN cells Embryo Homo sapiens (Human) CVCL_Y105
EPN1 cells Embryo Homo sapiens (Human) N.A.
EPN7 cells Embryo Homo sapiens (Human) N.A.
EPN7R cells Embryo Homo sapiens (Human) N.A.
DKFZ-EP1 cells Embryo Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).
Key Molecule: Multidrug resistance protein 1 (ABCB1) [11]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Ependymoma [ICD-11: 2A00.05]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell migration Activation hsa04670
Cell invasion Activation hsa05200
In Vitro Model BXD-1425EPN cells Embryo Homo sapiens (Human) CVCL_Y105
EPN1 cells Embryo Homo sapiens (Human) N.A.
EPN7 cells Embryo Homo sapiens (Human) N.A.
EPN7R cells Embryo Homo sapiens (Human) N.A.
DKFZ-EP1 cells Embryo Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description ABCB1 gene expression was observed in 4 out of 5 paediatric ependymoma cell lines and increased in stem cell enriched neurospheres. Functional inhibition of ABCB1 using vardenafil or verapamil significantly (p < 0.05-0.001) potentiated the response to three chemotherapeutic drugs (vincristine, etoposide and methotrexate). Both inhibitors were also able to significantly reduce migration (p < 0.001) and invasion (p < 0.001).
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Potassium voltage-gated channel subfamily H member 1 (KCNH1) [18]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Glioblastoma [ICD-11: 2A00.02]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell invasion Inhibition hsa05200
Cell proliferation Inhibition hsa05200
In Vitro Model U251 cells Brain Homo sapiens (Human) CVCL_0021
U251AR cells Brain Homo sapiens (Human) CVCL_1G29
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description EAG1 channel might be involved in cell-cycle progression of tumour cells because a significant reduction in the proliferation of tumour cell lines could be achieved by inhibiting EAG1 expression using antisense oligonucleotides. Ectopic expression of miR-296-3p reduced EAG1 expression and suppressed cell proliferation drug resistance.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [19]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Neuroblastoma [ICD-11: 2A00.11]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model Kelly cells Adrenal Homo sapiens (Human) CVCL_2092
Sk-N-AS cells Adrenal Homo sapiens (Human) CVCL_1700
SH-SY5Y cells Abdomen Homo sapiens (Human) CVCL_0019
In Vivo Model Orthotopic xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-204 direct targeting of the 3' UTR of BCL2 and NTRk2 (TrkB). BCL2 has a critical role in ensuring the survival of early developing cell types, NTRk2 is also a well-established pro-survival oncogene in neuroblastoma, signalling the activation of the PI3k/AkT pathway, a significant mechanism of drug resistance in neuroblastoma. Ectopic miR-204 expression significantly increased sensitivity to cisplatin and etoposide in vitro.
Key Molecule: BDNF/NT-3 growth factors receptor (NTRK2) [19]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Neuroblastoma [ICD-11: 2A00.11]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model Kelly cells Adrenal Homo sapiens (Human) CVCL_2092
Sk-N-AS cells Adrenal Homo sapiens (Human) CVCL_1700
SH-SY5Y cells Abdomen Homo sapiens (Human) CVCL_0019
In Vivo Model Orthotopic xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-204 direct targeting of the 3' UTR of BCL2 and NTRk2 (TrkB). BCL2 has a critical role in ensuring the survival of early developing cell types, NTRk2 is also a well-established pro-survival oncogene in neuroblastoma, signalling the activation of the PI3k/AkT pathway, a significant mechanism of drug resistance in neuroblastoma. Ectopic miR-204 expression significantly increased sensitivity to cisplatin and etoposide in vitro.
Mature B-cell neoplasms/lymphoma [ICD-11: 2A85]
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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-17-92 [15]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Mantle cell lymphoma [ICD-11: 2A85.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT signaling pathway Activation hsa04151
In Vitro Model Jeko-1 cells Blood Homo sapiens (Human) CVCL_1865
Granta-519 cells Blood Homo sapiens (Human) CVCL_1818
Z138c cells Blood Homo sapiens (Human) CVCL_B077
In Vivo Model CB-17/SCID nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 Xenograft experiments assay
Mechanism Description The protein phosphatase PHLPP2, an important negative regulator of the PI3k/AkT pathway, was a direct target of miR-17 92 miRNAs, miRNA-17 92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3k/AkT pathway activation.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: PH domain leucine-rich repeat-containing protein phosphatase 2 (PHLPP2) [15]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Mantle cell lymphoma [ICD-11: 2A85.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
PI3K/AKT signaling pathway Activation hsa04151
In Vitro Model Jeko-1 cells Blood Homo sapiens (Human) CVCL_1865
Granta-519 cells Blood Homo sapiens (Human) CVCL_1818
Z138c cells Blood Homo sapiens (Human) CVCL_B077
In Vivo Model CB-17/SCID nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Luciferase assay
Experiment for
Drug Resistance		 Xenograft experiments assay
Mechanism Description The protein phosphatase PHLPP2, an important negative regulator of the PI3k/AkT pathway, was a direct target of miR-17 92 miRNAs, miRNA-17 92 cluster mediates chemoresistance and enhances tumor growth in mantle cell lymphoma via PI3k/AkT pathway activation.
Acute lymphocytic leukemia [ICD-11: 2B33]
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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-485-3p [20]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Lymphocytic leukemia [ICD-11: 2B33.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model CEM cells Pleural effusion Homo sapiens (Human) N.A.
CEM/VM-1-5 cells Lymph Homo sapiens (Human) CVCL_1B35
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-485-3p expression can mediate etoposide sensitivity indirectly by fine-tuning Top2alpha expression through the modification of NF-YB expression. Accordingly, miR-485-3p can be a putative therapeutic target to modulate etoposide resistance in tumor cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Nuclear transcription factor Y subunit beta (NFYB) [20]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lymphocytic leukemia [ICD-11: 2B33.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model CEM cells Pleural effusion Homo sapiens (Human) N.A.
CEM/VM-1-5 cells Lymph Homo sapiens (Human) CVCL_1B35
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-485-3p expression can mediate etoposide sensitivity indirectly by fine-tuning Top2alpha expression through the modification of NF-YB expression. Accordingly, miR-485-3p can be a putative therapeutic target to modulate etoposide resistance in tumor cells.
Osteosarcoma [ICD-11: 2B51]
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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 [21], [22]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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 [23]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [22]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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 [16]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [23]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [21]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [16]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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 [24]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [24]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [24]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [26]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Osteosarcoma [ICD-11: 2B51.0]
 Disease Info 
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.
Ewing sarcoma [ICD-11: 2B52]
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-125b [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Ewing sarcoma [ICD-11: 2B52.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR125b-p53/BAKT signaling pathway Activation hsa05206
In Vitro Model RD-ES cells Bones Homo sapiens (Human) CVCL_2169
Sk-ES cells Bones Homo sapiens (Human) CVCL_0627
Sk-N-MC cells Bones Homo sapiens (Human) CVCL_0530
TC-71 cells Bones Homo sapiens (Human) CVCL_2213
VH-64 cells Bones Homo sapiens (Human) CVCL_9672
WE-68 cells Bones Homo sapiens (Human) CVCL_9717
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Celltiter-glo luminescent cell viability assay
Mechanism Description miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Cellular tumor antigen p53 (TP53) [2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Ewing sarcoma [ICD-11: 2B52.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR125b-p53/BAKT signaling pathway Activation hsa05206
In Vitro Model RD-ES cells Bones Homo sapiens (Human) CVCL_2169
Sk-ES cells Bones Homo sapiens (Human) CVCL_0627
Sk-N-MC cells Bones Homo sapiens (Human) CVCL_0530
TC-71 cells Bones Homo sapiens (Human) CVCL_2213
VH-64 cells Bones Homo sapiens (Human) CVCL_9672
WE-68 cells Bones Homo sapiens (Human) CVCL_9717
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Celltiter-glo luminescent cell viability assay
Mechanism Description miR-125b led to the development of chemoresistance by suppressing the expression of p53 and Bak, and repression of miR-125b sensitized EWS cells to apoptosis induced by treatment with various cytotoxic drugs.
Gastric cancer [ICD-11: 2B72]
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-181 [27]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Gastric adenocarcinoma [ICD-11: 2B72.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
SGC7901/VCR cells Gastric Homo sapiens (Human) CVCL_VU58
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.
Key Molecule: hsa-mir-15b [28]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Mitochondrial signaling pathway Activation hsa04217
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
SGC7901/VCR cells Gastric Homo sapiens (Human) CVCL_VU58
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.
Key Molecule: hsa-mir-16 [28]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Mitochondrial signaling pathway Activation hsa04217
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
SGC7901/VCR cells Gastric Homo sapiens (Human) CVCL_VU58
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [27]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Gastric adenocarcinoma [ICD-11: 2B72.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
SGC7901/VCR cells Gastric Homo sapiens (Human) CVCL_VU58
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [28]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Mitochondrial signaling pathway Activation hsa04217
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
SGC7901/VCR cells Gastric Homo sapiens (Human) CVCL_VU58
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-15b and miR-16, among the downregulated miRNAs in SGC7901/VCR cells, were demonstrated to play a role in the development of MDR in gastric cancer cells by targeting the antiapoptotic gene BCL2.
Colon cancer [ICD-11: 2B90]
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-424 [13]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Colon cancer [ICD-11: 2B90.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
U251 cells Brain Homo sapiens (Human) CVCL_0021
HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
PARP cells Skin Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Hypoxia induces miR-424 expression and that miR-424 in turn suppresses the level of PDCD4 protein, a tumor suppressor that is involved in apoptosis, by targeting its 3' untranslated region. Functionally, miR-424 overexpression decreases the sensitivity of cancer cells (HCT116 and A375) to doxorubicin (Dox) and etoposide. In contrast, the inhibition of miR-424 (+) apoptosis and increased the sensitivity of cancer cells to Dox. In a xenograft tumor model, miR-424 overexpression promoted tumor growth following Dox treatment, suggesting that miR-424 promotes tumor cell resistance to Dox. Furthermore, miR-424 levels are inversely correlated with PDCD4 expression in clinical breast cancer samples.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Programmed cell death protein 4 (PDCD4) [13]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Colon cancer [ICD-11: 2B90.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
U251 cells Brain Homo sapiens (Human) CVCL_0021
HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
PARP cells Skin Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Hypoxia induces miR-424 expression and that miR-424 in turn suppresses the level of PDCD4 protein, a tumor suppressor that is involved in apoptosis, by targeting its 3' untranslated region. Functionally, miR-424 overexpression decreases the sensitivity of cancer cells (HCT116 and A375) to doxorubicin (Dox) and etoposide. In contrast, the inhibition of miR-424 (+) apoptosis and increased the sensitivity of cancer cells to Dox. In a xenograft tumor model, miR-424 overexpression promoted tumor growth following Dox treatment, suggesting that miR-424 promotes tumor cell resistance to Dox. Furthermore, miR-424 levels are inversely correlated with PDCD4 expression in clinical breast cancer samples.
Liver cancer [ICD-11: 2C12]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Cytochrome P450 family 1 subfamily B member1 (CYP1B1) [29]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Liver cancer [ICD-11: 2C12.6]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation miR27b/CCNG1/p53 signaling pathway Regulation hsa05206
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
SNU182 cells Liver Homo sapiens (Human) CVCL_0090
SNU-739 cells Liver Homo sapiens (Human) CVCL_5088
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo luminescent cell viability assay
Mechanism Description miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-196b [30]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
c-Myc signaling pathway Activation hsa05230
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-196b overexpression decreased IGF2BP1 RNA expression and protein level. The IGF2BP1 down-regulation by either miR-196b or IGF2BP1 siRNA led to an increase in apoptosis and a decrease in cell viability and proliferation in normal culture conditions. However, IGF2BP1 silencing did not modify the chemoresistance induced by hypoxia, probably because it is not the only target of miR-196b involved in the regulation of apoptosis.
Key Molecule: hsa-mir-27b [29]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Liver cancer [ICD-11: 2C12.6]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation miR27b/CCNG1/p53 signaling pathway Regulation hsa05206
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
SNU182 cells Liver Homo sapiens (Human) CVCL_0090
SNU-739 cells Liver Homo sapiens (Human) CVCL_5088
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 CellTiter-Glo luminescent cell viability assay
Mechanism Description miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
Key Molecule: hsa-mir-23a [31]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
MHCC97-L cells Liver Homo sapiens (Human) CVCL_4973
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of miR-23a could significantly potentiate the in vitro and in vivo anti-tumor effect of etoposide; miR-23a could directly bind to 3'untranslated region of TOP1 mRNA, and suppress the corresponding protein expression and inhibition of miR-23a further arguments the expression of TOP1. Suppression of TOP1 expression by miR-23a results in reduction of overall intracellular topoisomerase activity when the cells are exposed to etoposide, which in consequence enhances drug response of HCC cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) [30]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
c-Myc signaling pathway Activation hsa05230
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR; Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-196b overexpression decreased IGF2BP1 RNA expression and protein level. The IGF2BP1 down-regulation by either miR-196b or IGF2BP1 siRNA led to an increase in apoptosis and a decrease in cell viability and proliferation in normal culture conditions. However, IGF2BP1 silencing did not modify the chemoresistance induced by hypoxia, probably because it is not the only target of miR-196b involved in the regulation of apoptosis.
Key Molecule: Cyclin-G1 (CCNG1) [29]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Liver cancer [ICD-11: 2C12.6]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
miR27b/CCNG1/p53 signaling pathway Regulation hsa05206
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
SNU182 cells Liver Homo sapiens (Human) CVCL_0090
SNU-739 cells Liver Homo sapiens (Human) CVCL_5088
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo luminescent cell viability assay
Mechanism Description miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
Key Molecule: DNA topoisomerase 1 (TOP1) [31]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model HepG2 cells Liver Homo sapiens (Human) CVCL_0027
MHCC97-L cells Liver Homo sapiens (Human) CVCL_4973
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Luciferase assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of miR-23a could significantly potentiate the in vitro and in vivo anti-tumor effect of etoposide; miR-23a could directly bind to 3'untranslated region of TOP1 mRNA, and suppress the corresponding protein expression and inhibition of miR-23a further arguments the expression of TOP1. Suppression of TOP1 expression by miR-23a results in reduction of overall intracellular topoisomerase activity when the cells are exposed to etoposide, which in consequence enhances drug response of HCC cells.
Laryngeal cancer [ICD-11: 2C23]
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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-125a [32]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Laryngeal cancer [ICD-11: 2C23.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEp-2 cells Skin Homo sapiens (Human) CVCL_1906
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay; Annexin V-FITC apoptosis assay
Mechanism Description Inhibition of HAX-1 by miR125a reverses cisplatin resistance in laryngeal cancer stem cells. Overexpression of miR125a increases the sensitivity of Hep-2-CSCs to cisplatin by inhibiting HAX-1.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: HCLS1-associated protein X-1 (HAX1) [32]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Laryngeal cancer [ICD-11: 2C23.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEp-2 cells Skin Homo sapiens (Human) CVCL_1906
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; Luciferase reporter assay
Experiment for
Drug Resistance		 MTT assay; Annexin V-FITC apoptosis assay
Mechanism Description Inhibition of HAX-1 by miR125a reverses cisplatin resistance in laryngeal cancer stem cells. Overexpression of miR125a increases the sensitivity of Hep-2-CSCs to cisplatin by inhibiting HAX-1.
Lung cancer [ICD-11: 2C25]
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: HOX transcript antisense RNA (HOTAIR) [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model NCI-H446 cells Lung Homo sapiens (Human) CVCL_1562
NCI-H69 cells Lung Homo sapiens (Human) CVCL_1579
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description H3kH3k27me3 induces multidrug resistance in small cell lung cancer by affecting HOXA1 DNA methylation via regulation of the LncRNA HOTAIR.
Key Molecule: hsa-mir-216a [33]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model 16HBE cells Lung Homo sapiens (Human) CVCL_0112
H446 cells Lung Homo sapiens (Human) CVCL_1562
H69 cells Lung Homo sapiens (Human) CVCL_8121
H69AR cells Lung Homo sapiens (Human) CVCL_3513
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR216a.
Key Molecule: hsa-mir-100 [6]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model NCI-H69 cells Lung Homo sapiens (Human) CVCL_1579
NCI-H69AR cells Lung Homo sapiens (Human) CVCL_3513
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Forced expression of HOXA1 in immortalised human mammary epithelial cells results in oncogenic transformation and tumour formation in vivo. HOXA1 expression was inversely correlated with miR-100. HOXA1-mediated SCLC chemoresistance is under the regulation of miR-100. HOXA1 may be a prognostic predictor and potential therapeutic target in human SCLC.
Key Molecule: H19, imprinted maternally expressed transcript (H19) [34]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
MCF-7/AdrVp cells Breast Homo sapiens (Human) CVCL_4Y46
Experiment for
Molecule Alteration		 RT-PCR; Northern blotting analysis
Experiment for
Drug Resistance		 Clonogenic assay
Mechanism Description The mRNA of the H19 gene is overexpressed in MCF-7/AdrVp cells relative toparental MCF-7 cells or drug-sensitive MCF-7/AdrVp revertant cells. H19is an imprinted gene with an important role in fetal differentiation, as well as a postulated function as a tumor suppressor gene. Another p95-over-expressing multidrug-resistant cell line, human lung carcinoma NCI-H1688, also displays high levels of 1119 mRNA.
       Regulation by the Disease Microenvironment (RTDM) Click to Show/Hide
Key Molecule: HOXA distal transcript antisense RNA (HOTTIP) [33]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model 16HBE cells Lung Homo sapiens (Human) CVCL_0112
H446 cells Lung Homo sapiens (Human) CVCL_1562
H69 cells Lung Homo sapiens (Human) CVCL_8121
H69AR cells Lung Homo sapiens (Human) CVCL_3513
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description HOTTIP acts as sponge of miR216a and enhanced the expression of its another target gene, anti-apoptotic gene BCL-2.
Key Molecule: hsa-mir-495 [14]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NCI-H446 cells Lung Homo sapiens (Human) CVCL_1562
NCI-H69 cells Lung Homo sapiens (Human) CVCL_1579
H69/AR cells Lung Homo sapiens (Human) CVCL_3513
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Cell scratch-wound healing assay; Flow cytometry assay
Mechanism Description miR495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX. Ectopic expression of Etk/BMX obviously rescued the miR495 elevation elevation-induced inhibition of drug resistance.
Key Molecule: Ephrin type-A receptor 3 (EPHA3) [14]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NCI-H446 cells Lung Homo sapiens (Human) CVCL_1562
NCI-H69 cells Lung Homo sapiens (Human) CVCL_1579
H69/AR cells Lung Homo sapiens (Human) CVCL_3513
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunohistochemical staining; Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Cell scratch-wound healing assay; Flow cytometry assay
Mechanism Description miR495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX. Ectopic expression of Etk/BMX obviously rescued the miR495 elevation elevation-induced inhibition of drug resistance.
Key Molecule: Cytoplasmic tyrosine-protein kinase BMX (BMX) [14]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model NCI-H446 cells Lung Homo sapiens (Human) CVCL_1562
NCI-H69 cells Lung Homo sapiens (Human) CVCL_1579
H69/AR cells Lung Homo sapiens (Human) CVCL_3513
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Immunohistochemical staining; Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Cell scratch-wound healing assay; Flow cytometry assay
Mechanism Description miR495 promotes the chemoresistance of SCLC through the epithelial-mesenchymal transition via Etk/BMX. Ectopic expression of Etk/BMX obviously rescued the miR495 elevation elevation-induced inhibition of drug resistance.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: H3 lysine 27 trimethylation (H3K27) [1]
Molecule Alteration Methylation
Up-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model NCI-H446 cells Lung Homo sapiens (Human) CVCL_1562
NCI-H69 cells Lung Homo sapiens (Human) CVCL_1579
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description H3kH3k27me3 induces multidrug resistance in small cell lung cancer by affecting HOXA1 DNA methylation via regulation of the LncRNA HOTAIR.
Key Molecule: Homeobox protein Hox-A13 (HOXA13) [33]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model 16HBE cells Lung Homo sapiens (Human) CVCL_0112
H446 cells Lung Homo sapiens (Human) CVCL_1562
H69 cells Lung Homo sapiens (Human) CVCL_8121
H69AR cells Lung Homo sapiens (Human) CVCL_3513
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis; RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description HOTTIP acts at least partly by controlling HOXA13 in SCLC poor prognostic and chemoresistance progression.
Key Molecule: Homeobox protein Hox-A1 (HOXA1) [6]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model NCI-H69 cells Lung Homo sapiens (Human) CVCL_1579
NCI-H69AR cells Lung Homo sapiens (Human) CVCL_3513
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Forced expression of HOXA1 in immortalised human mammary epithelial cells results in oncogenic transformation and tumour formation in vivo. HOXA1 expression was inversely correlated with miR-100. HOXA1-mediated SCLC chemoresistance is under the regulation of miR-100. HOXA1 may be a prognostic predictor and potential therapeutic target in human SCLC.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Apoptosis regulator Bcl-2 (BCL2) [33]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model 16HBE cells Lung Homo sapiens (Human) CVCL_0112
H446 cells Lung Homo sapiens (Human) CVCL_1562
H69 cells Lung Homo sapiens (Human) CVCL_8121
H69AR cells Lung Homo sapiens (Human) CVCL_3513
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Luciferase reporter assay; RT-qPCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Long non-coding RNA HOTTIP promotes BCL-2 expression and induces chemoresistance in small cell lung cancer by sponging miR216a.
Key Molecule: hsa-miR-30a-5p [35]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model H446 cells Lung Homo sapiens (Human) CVCL_1562
Letp cells Lung Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; WB assay; Colony formation assay; Fow cytometric analysis
Mechanism Description Beclin-1-dependent autophagy in SCLC was directly regulated by miR30a-5p. miR30a-5p contributed to chemoresistance of SCLC cells partially in an Beclin-1-dependent manneRNA.
Key Molecule: hsa-mir-335 [36]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model H69 cells Lung Homo sapiens (Human) CVCL_8121
H69AR cells Lung Homo sapiens (Human) CVCL_3513
H446 cells Lung Homo sapiens (Human) CVCL_1562
H446/DDP cells Lung Homo sapiens (Human) CVCL_RT21
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Annexin V-PE Apoptosis assay; Flow cytometry assay; Wound healing assay; Colony formation assay
Mechanism Description Overexpression of miR335 sensitized human SCLC cells to chemotherapy and radiotherapy, promoted cell apoptosis and inhibited cell migration ability of human SCLC in vitro, and inhibited tumor growth in vivo. Overexpression of miR335 decreased the expression of PARP-1 mRNA and protein, and NF-kB protein levels were correspondingly downregulated, thus regulating the chemo-radiosensitivity of SCLC.
Key Molecule: hsa-miR-662 [37]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung squamous cell carcinoma [ICD-11: 2C25.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model H1703 cells Lung Homo sapiens (Human) CVCL_1490
NCI-H520 cells Lung Homo sapiens (Human) CVCL_1566
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-192 and miR-662 enhance chemoresistance and invasiveness of squamous cell lung carcinoma.
Key Molecule: hsa-mir-494 [38]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation BCL2 signaling pathway Activation hsa04210
Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model H69 cells Lung Homo sapiens (Human) CVCL_8121
H446 cells Lung Homo sapiens (Human) CVCL_1562
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description Knockdown of SCGN led to significantly increasing of chemosensitivity, which is similar to those induced by miR-494 mimics, and ectopic expression of SCGN could rescue the suppressive effect of miR-494.
Key Molecule: hsa-mir-103 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
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 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
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-181 [27]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
A549/CDDP cells Lung Homo sapiens (Human) CVCL_0023
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Beclin-1 (BECN1) [35]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model H446 cells Lung Homo sapiens (Human) CVCL_1562
Letp cells Lung Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Luciferase reporter assay; Western blot analysis
Experiment for
Drug Resistance		 MTT assay; WB assay; Colony formation assay; Fow cytometric analysis
Mechanism Description Beclin-1-dependent autophagy in SCLC was directly regulated by miR30a-5p. miR30a-5p contributed to chemoresistance of SCLC cells partially in an Beclin-1-dependent manneRNA.
Key Molecule: Tetraspanin-12 (TSN12) [39]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model NCI-H446 cells Lung Homo sapiens (Human) CVCL_1562
NCI-H69 cells Lung Homo sapiens (Human) CVCL_1579
NCI-H69AR cells Lung Homo sapiens (Human) CVCL_3513
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Annexin V/propidium iodide detection assay; Scratch healing test
Mechanism Description TSPAN12 promotes chemoresistance and proliferation of SCLC under the regulation of miR495, and TSPAN12 is negatively regulated by miR495.
Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1) [36]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation NF-kappaB signaling pathway Inhibition hsa04064
In Vitro Model H69 cells Lung Homo sapiens (Human) CVCL_8121
H69AR cells Lung Homo sapiens (Human) CVCL_3513
H446 cells Lung Homo sapiens (Human) CVCL_1562
H446/DDP cells Lung Homo sapiens (Human) CVCL_RT21
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Annexin V-PE Apoptosis assay; Flow cytometry assay; Wound healing assay; Colony formation assay
Mechanism Description Overexpression of miR335 sensitized human SCLC cells to chemotherapy and radiotherapy, promoted cell apoptosis and inhibited cell migration ability of human SCLC in vitro, and inhibited tumor growth in vivo. Overexpression of miR335 decreased the expression of PARP-1 mRNA and protein, and NF-kB protein levels were correspondingly downregulated, thus regulating the chemo-radiosensitivity of SCLC.
Key Molecule: Secretagogin (SCGN) [38]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung small cell carcinoma [ICD-11: 2C25.2]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation BCL2 signaling pathway Activation hsa04210
Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model H69 cells Lung Homo sapiens (Human) CVCL_8121
H446 cells Lung Homo sapiens (Human) CVCL_1562
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometry assay
Mechanism Description Knockdown of SCGN led to significantly increasing of chemosensitivity, which is similar to those induced by miR-494 mimics, and ectopic expression of SCGN could rescue the suppressive effect of miR-494.
Key Molecule: DNA repair protein RAD51 homolog 1 (RAD51) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
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) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model H1299 cells Lung Homo sapiens (Human) CVCL_0060
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: Apoptosis regulator Bcl-2 (BCL2) [27]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Lung cancer [ICD-11: 2C25.5]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
A549/CDDP cells Lung Homo sapiens (Human) CVCL_0023
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description The antiapoptotic protein BCL2 is upregulated, whereas miR-181b is downregulated in both SGC7901/VCR and A549/CDDP cells, compared with SGC7901 and A549 cells, respectively. Enforced miR-181b expression reduced BCL2 protein level and sensitized SGC7901/VCR and A549/CDDP cells to VCR-induced and CDDP-induced apoptosis, respectively.
Melanoma [ICD-11: 2C30]
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-424 [13]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
U251 cells Brain Homo sapiens (Human) CVCL_0021
HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
PARP cells Skin Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Hypoxia induces miR-424 expression and that miR-424 in turn suppresses the level of PDCD4 protein, a tumor suppressor that is involved in apoptosis, by targeting its 3' untranslated region. Functionally, miR-424 overexpression decreases the sensitivity of cancer cells (HCT116 and A375) to doxorubicin (Dox) and etoposide. In contrast, the inhibition of miR-424 (+) apoptosis and increased the sensitivity of cancer cells to Dox. In a xenograft tumor model, miR-424 overexpression promoted tumor growth following Dox treatment, suggesting that miR-424 promotes tumor cell resistance to Dox. Furthermore, miR-424 levels are inversely correlated with PDCD4 expression in clinical breast cancer samples.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Programmed cell death protein 4 (PDCD4) [13]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Melanoma [ICD-11: 2C30.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell proliferation Activation hsa05200
In Vitro Model HCT116 cells Colon Homo sapiens (Human) CVCL_0291
A375 cells Skin Homo sapiens (Human) CVCL_0132
U251 cells Brain Homo sapiens (Human) CVCL_0021
HEK293T cells Kidney Homo sapiens (Human) CVCL_0063
PARP cells Skin Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Hypoxia induces miR-424 expression and that miR-424 in turn suppresses the level of PDCD4 protein, a tumor suppressor that is involved in apoptosis, by targeting its 3' untranslated region. Functionally, miR-424 overexpression decreases the sensitivity of cancer cells (HCT116 and A375) to doxorubicin (Dox) and etoposide. In contrast, the inhibition of miR-424 (+) apoptosis and increased the sensitivity of cancer cells to Dox. In a xenograft tumor model, miR-424 overexpression promoted tumor growth following Dox treatment, suggesting that miR-424 promotes tumor cell resistance to Dox. Furthermore, miR-424 levels are inversely correlated with PDCD4 expression in clinical breast cancer samples.
Merkel cell carcinoma [ICD-11: 2C34]
Click to Show/Hide
Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [7]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Merkel cell carcinoma [ICD-11: 2C34.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MKL-2 cells Peripheral blood Homo sapiens (Human) CVCL_D027
WaGa cells Ascites Homo sapiens (Human) CVCL_E998
MKL-1 cells Liver Homo sapiens (Human) CVCL_2600
MS-1 cells Lung Homo sapiens (Human) CVCL_IQ55
In Vivo Model NSG mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description These findings in patient specimens were consistent with the possibility that ABCB5+ MCC cells are preferentially resistant to treatment with the first-line chemotherapeutic agents, carboplatin and etoposide.
Key Molecule: ATP-binding cassette sub-family B5 (ABCB5) [7]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Merkel cell carcinoma [ICD-11: 2C34.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model MKL-2 cells Peripheral blood Homo sapiens (Human) CVCL_D027
WaGa cells Ascites Homo sapiens (Human) CVCL_E998
MKL-1 cells Liver Homo sapiens (Human) CVCL_2600
MS-1 cells Lung Homo sapiens (Human) CVCL_IQ55
In Vivo Model NSG mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR; Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description These findings in patient specimens were consistent with the possibility that ABCB5+ MCC cells are preferentially resistant to treatment with the first-line chemotherapeutic agents, carboplatin and etoposide.
Breast cancer [ICD-11: 2C60]
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-106b~25 [12]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR106b~25 cluster/EP300/E-cadherin signaling pathway Regulation hsa05206
In Vitro Model MTMECs cells Breast Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description miR-106b~25 cluster controls transporter-independent MDR by apoptosis evasion via downregulation of EP300.
Key Molecule: hsa-mir-128a [40]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR-128 regulates sensitivity to drugs and apoptosis in breast cancer cells, pro-apoptotic protein bax is negatively post-transcriptionally regulated by miR-128. Bax overexpression could lead to a generalised enhancement of the apoptotic response to death stimuli, miR-128 was significantly associated with a drug fast in breast cancer cells by resisting the activation of the apoptosis pathway.
Key Molecule: hsa-mir-155 [3]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
TGF-beta/Smad signaling pathway Regulation hsa04350
In Vitro Model Breast cancer cell lines Colon Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR; Northern blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Loss of FOXO3a is often linked to a decline in apoptotic activity and increased chemoresistance in cancer cells. miR-155 directly interacts with 3'-UTR of FOXO3a and blocks FOXO3a translation. knockdown of miR-155 renders cells to apoptosis and enhances chemosensitivity.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Histone acetyltransferase p300 (EP300) [12]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
miR106b~25 cluster/EP300/E-cadherin signaling pathway Regulation hsa05206
In Vitro Model MTMECs cells Breast Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 Flow cytometry assay
Mechanism Description miR-106b~25 cluster controls transporter-independent MDR by apoptosis evasion via downregulation of EP300.
Key Molecule: Apoptosis regulator BAX (BAX) [40]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
Experiment for
Molecule Alteration		 luciferase report assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR-128 regulates sensitivity to drugs and apoptosis in breast cancer cells, pro-apoptotic protein bax is negatively post-transcriptionally regulated by miR-128. Bax overexpression could lead to a generalised enhancement of the apoptotic response to death stimuli, miR-128 was significantly associated with a drug fast in breast cancer cells by resisting the activation of the apoptosis pathway.
Key Molecule: Forkhead box protein O3 (FOXO3) [3]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
TGF-beta/Smad signaling pathway Regulation hsa04350
In Vitro Model Breast cancer cell lines Colon Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Loss of FOXO3a is often linked to a decline in apoptotic activity and increased chemoresistance in cancer cells. miR-155 directly interacts with 3'-UTR of FOXO3a and blocks FOXO3a translation. knockdown of miR-155 renders cells to apoptosis and enhances chemosensitivity.
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 [24]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
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 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
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 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
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-326 [41]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 RT-PCR; qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The elevated levels of miR-326 in the mimics-transfected VP-16-resistant cell line, MCF-7/VP, downregulated MRP-1 expression and sensitized these cells to VP-16 and doxorubicin.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [41]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description The elevated levels of miR-326 in the mimics-transfected VP-16-resistant cell line, MCF-7/VP, downregulated MRP-1 expression and sensitized these cells to VP-16 and doxorubicin.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: ATM interactor (ATMIN) [24]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
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) [24]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
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) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
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) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model MDA-MB-231 cells Breast Homo sapiens (Human) CVCL_0062
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.
Ovarian cancer [ICD-11: 2C73]
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-103 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model PEO1 C4-2 cells Ovary Homo sapiens (Human) N.A.
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 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model PEO1 C4-2 cells Ovary Homo sapiens (Human) N.A.
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: DNA repair protein RAD51 homolog 1 (RAD51) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model PEO1 C4-2 cells Ovary Homo sapiens (Human) N.A.
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) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Ovarian cancer [ICD-11: 2C73.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model PEO1 C4-2 cells Ovary Homo sapiens (Human) N.A.
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.
Cervical cancer [ICD-11: 2C77]
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-103 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Cervical cancer [ICD-11: 2C77.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
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 [25]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Cervical cancer [ICD-11: 2C77.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
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: DNA repair protein RAD51 homolog 1 (RAD51) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Cervical cancer [ICD-11: 2C77.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
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) [25]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Cervical cancer [ICD-11: 2C77.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
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.
Kidney cancer [ICD-11: 2C90]
Click to Show/Hide
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Drug Inactivation by Structure Modification (DISM) Click to Show/Hide
Key Molecule: Cytochrome P450 family 1 subfamily B member1 (CYP1B1) [29]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Kidney cancer [ICD-11: 2C90.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation miR27b/CCNG1/p53 signaling pathway Regulation hsa05206
In Vitro Model 769-P cells Kidney Homo sapiens (Human) CVCL_1050
786-O cells Kidney Homo sapiens (Human) CVCL_1051
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo luminescent cell viability assay
Mechanism Description miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-27b [29]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Kidney cancer [ICD-11: 2C90.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation miR27b/CCNG1/p53 signaling pathway Regulation hsa05206
In Vitro Model 769-P cells Kidney Homo sapiens (Human) CVCL_1050
786-O cells Kidney Homo sapiens (Human) CVCL_1051
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qPCR
Experiment for
Drug Resistance		 CellTiter-Glo luminescent cell viability assay
Mechanism Description miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Cyclin-G1 (CCNG1) [29]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Kidney cancer [ICD-11: 2C90.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
miR27b/CCNG1/p53 signaling pathway Regulation hsa05206
In Vitro Model 769-P cells Kidney Homo sapiens (Human) CVCL_1050
786-O cells Kidney Homo sapiens (Human) CVCL_1051
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CellTiter-Glo luminescent cell viability assay
Mechanism Description miR-27b synergizes with anticancer drugs througth enhancing anticancer drug-induced cell death which due to p53 activation and CYP1B1 suppression.
Retina cancer [ICD-11: 2D02]
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-34 [42]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Retinoblastoma [ICD-11: 2D02.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
MAGE-A/p53 signaling pathway Regulation hsa04115
In Vitro Model HXO-Rb44 cells Retina Homo sapiens (Human) CVCL_D542
SO-Rb50 cells Retina Homo sapiens (Human) CVCL_D543
WERI-Rb-1 cells Retina Homo sapiens (Human) CVCL_1792
Y79 cells Retina Homo sapiens (Human) CVCL_1893
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 Freedom Evolyzer-2200 Enzyme-Linked Immunometric meter; Flow cytometry assay
Mechanism Description miR-34a may function as a tumor suppressor for RB by targeting MAGE-A and upregulating p53 expression to enhance cell apoptosis and chemosensitivity (Carboplatin; Etoposide; Adriamycin; vincristine).
Key Molecule: hsa-miR-3163 [43]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Retinoblastoma [ICD-11: 2D02.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model WERI-Rb-1 cells Retina Homo sapiens (Human) CVCL_1792
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Silencing of ABCG2 by MicroRNA-3163 inhibits multidrug resistance in retinoblastoma cancer stem cells.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [43]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Retinoblastoma [ICD-11: 2D02.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
In Vitro Model WERI-Rb-1 cells Retina Homo sapiens (Human) CVCL_1792
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description Silencing of ABCG2 by MicroRNA-3163 inhibits multidrug resistance in retinoblastoma cancer stem cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Melanoma antigen A 4 (MAGE4) [42]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Retinoblastoma [ICD-11: 2D02.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
MAGE-A/p53 signaling pathway Regulation hsa04115
In Vitro Model HXO-Rb44 cells Retina Homo sapiens (Human) CVCL_D542
SO-Rb50 cells Retina Homo sapiens (Human) CVCL_D543
WERI-Rb-1 cells Retina Homo sapiens (Human) CVCL_1792
Y79 cells Retina Homo sapiens (Human) CVCL_1893
Experiment for
Molecule Alteration		 Western blot analysis; RT-qPCR
Experiment for
Drug Resistance		 Freedom Evolyzer-2200 Enzyme-Linked Immunometric meter; Flow cytometry assay
Mechanism Description miR-34a may function as a tumor suppressor for RB by targeting MAGE-A and upregulating p53 expression to enhance cell apoptosis and chemosensitivity (Carboplatin; Etoposide; Adriamycin; vincristine).
Head and neck cancer [ICD-11: 2D42]
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: Interleukin 2 receptor subunit alpha (IL2RA) [4]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Head and neck squamous cell carcinoma [ICD-11: 2D42.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model PCI-13 cells Ovary Homo sapiens (Human) CVCL_C182
Experiment for
Molecule Alteration		 Western blotting assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description IL-2Ralpha-expressing cells were significantly more resistant to apoptosis induction by a tripeptidyl proteasome inhibitor (ALLN) and two chemotherapeutic drugs (VP-16 and taxol) than the control or IL-2Rgamma+ cells.IL-2Ralpha overexpression increases cell proliferation rate associated with increasing levels of cell cycle regulatory proteins.
Cervix epitheloid carcinoma [ICD-11: 2E66]
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-29b [44]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Negroid cervix epitheloid carcinoma [ICD-11: 2E66.Y]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 xCELLigence cell viability assay; Flow cytometry assay; Caspase-3 activity assay
Mechanism Description microRNA hsa-miR29b potentiates etoposide toxicity in HeLa cells via down-regulation of Mcl-1.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Induced myeloid leukemia cell differentiation protein Mcl-1 (MCL1) [44]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Negroid cervix epitheloid carcinoma [ICD-11: 2E66.Y]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 xCELLigence cell viability assay; Flow cytometry assay; Caspase-3 activity assay
Mechanism Description microRNA hsa-miR29b potentiates etoposide toxicity in HeLa cells via down-regulation of Mcl-1.
Pituitary cancer [ICD-11: 2F37]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Bcl-2-associated agonist of cell death (BAD) [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: Baculoviral IAP repeat containing 2 (BIRC2) [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: Baculoviral IAP repeat-containing protein 1 (BIRC1) [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Key Molecule: E3 ubiquitin-protein ligase XIAP (XIAP) [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Pituitary adenoma [ICD-11: 2F37.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Pituitary tumour stem-like cells Pituitary Homo sapiens (Human) N.A.
In Vivo Model NOD/SCID mice xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 WST-1 proliferation assay
Mechanism Description Stem cells are generally known to preferentially express antiapoptotic genes, such as BCL-2, cIAP1, NAIP, and XIAP.The expression levels of these antiapoptotic genes in PASC1 were one- to sixfolds higher than those in its daughter cells.
Peripheral nerve sheath tumor [ICD-11: 2F3Y]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Neurofibromin (NF1) [8]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Peripheral nerve sheath tumor [ICD-11: 2F3Y.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation RAS signaling pathway Activation hsa04014
In Vitro Model sNF02.2 cells Lung Homo sapiens (Human) CVCL_K280
Hs 53.T cells Skin Homo sapiens (Human) CVCL_0786
Experiment for
Molecule Alteration		 qRT-PCR; Western blotting assay
Experiment for
Drug Resistance		 Ez-Cytox assay
Mechanism Description High expression of Bcl-xL in the MPNST cells was caused by a decreased transcriptional expression of the NF1 gene. Down-regulation of the NF1 gene by RNA interference (RNAi) induced an increase in Bcl-xL expression and a decrease in its sensitivity to apoptosis in the benign neurofibroma cell line and primary normal cells.
ICD-14: Skin diseases
Click to Show/Hide the Resistance Disease of This Class
Keloid/hypertrophic scars [ICD-11: EE60]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance-associated protein 1 (MRP1) [5]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Hypertrophic scar [ICD-11: EE60.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Hypertrophic scar tissue isolates N.A.
Experiment for
Molecule Alteration		 Western blotting assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts.
Key Molecule: Multidrug resistance protein 1 (ABCB1) [5]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Hypertrophic scar [ICD-11: EE60.0]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
In Vitro Model Hypertrophic scar tissue isolates N.A.
Experiment for
Molecule Alteration		 Western blotting assay
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Fibroblasts derived from hypertrophic scar and normal skin tissues were first compared for their resistance to verapamil and etoposide phosphate. Scar fibroblasts showed stronger resistance to both verapamil and etoposide than normal fibroblasts, also scar fibroblasts expressed more P-glycoprotein and MRP1 than normal fibroblasts.
References
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