Drug Information

Drug (ID: DG00503) and It's Reported Resistant Information
Name
TRAIL
Synonyms
Tumor necrosis factor-related apoptosis-inducing ligand
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Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (5 diseases)
Cervical cancer [ICD-11: 2C77]
[1]
Gastric cancer [ICD-11: 2B72]
[1]
Liver cancer [ICD-11: 2C12]
[1]
Lung cancer [ICD-11: 2C25]
[2]
Pancreatic cancer [ICD-11: 2C10]
[3]
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  UAPP: Unusual Activation of Pro-survival Pathway
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
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Acute myeloid leukemia [ICD-11: 2A60]
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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-27a [4]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 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 HL60 cells Peripheral blood Homo sapiens (Human) CVCL_0002
K562 cells Blood Homo sapiens (Human) CVCL_0004
K562/A02 cells Blood Homo sapiens (Human) CVCL_0368
NB4 cells Bone marrow Homo sapiens (Human) CVCL_0005
HL-60/ADR cells Blood Homo sapiens (Human) CVCL_0304
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR-424 and miR-27a increase TRAIL sensitivity of acute myeloid leukemia by targeting PLAG1.
Key Molecule: hsa-mir-424 [4]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 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 HL60 cells Peripheral blood Homo sapiens (Human) CVCL_0002
K562 cells Blood Homo sapiens (Human) CVCL_0004
K562/A02 cells Blood Homo sapiens (Human) CVCL_0368
NB4 cells Bone marrow Homo sapiens (Human) CVCL_0005
HL-60/ADR cells Blood Homo sapiens (Human) CVCL_0304
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR-424 and miR-27a increase TRAIL sensitivity of acute myeloid leukemia by targeting PLAG1.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Zinc finger protein PLAG1 (PLAG1) [4]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 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 HL60 cells Peripheral blood Homo sapiens (Human) CVCL_0002
K562 cells Blood Homo sapiens (Human) CVCL_0004
K562/A02 cells Blood Homo sapiens (Human) CVCL_0368
NB4 cells Bone marrow Homo sapiens (Human) CVCL_0005
HL-60/ADR cells Blood Homo sapiens (Human) CVCL_0304
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR-424 and miR-27a increase TRAIL sensitivity of acute myeloid leukemia by targeting PLAG1.
Gastric cancer [ICD-11: 2B72]
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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-942 [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
In Vitro Model HGC27 cells Gastric Homo sapiens (Human) CVCL_1279
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interferon alpha-inducible protein 27 (IFI27) [1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Gastric cancer [ICD-11: 2B72.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
In Vitro Model HGC27 cells Gastric Homo sapiens (Human) CVCL_1279
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-494 [5]
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
Cell viability Inhibition hsa05200
In Vitro Model BGC-823 cells Gastric Homo sapiens (Human) CVCL_3360
MGC-803 cells Gastric Homo sapiens (Human) CVCL_5334
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Down-regulation of Survivin.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Baculoviral IAP repeat-containing protein 5 (BIRC5) [5]
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
Cell viability Inhibition hsa05200
In Vitro Model BGC-823 cells Gastric Homo sapiens (Human) CVCL_3360
MGC-803 cells Gastric Homo sapiens (Human) CVCL_5334
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Down-regulation of Survivin.
Colorectal cancer [ICD-11: 2B91]
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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-27a [6]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
FHC cells Colon Homo sapiens (Human) CVCL_3688
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometric analysis
Mechanism Description Knockdown of miR27a sensitizes colorectal cancer stem cells to TRAIL by promoting the formation of Apaf-1-caspase-9 complex. miR27a antioligonucleotides enhanced the anti-tumor effect of TRAIL on colorectal cancer stem cells via increasing the expression of Apaf-1.
Key Molecule: hsa-mir-20a [7]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation TBID/Mitochondria signaling pathway Activation hsa04217
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
SW948 cells Colon Homo sapiens (Human) CVCL_0632
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay; FITC-Annexin V and propidium iodide (PI) assay
Mechanism Description The knockdown of miR20a inhibited the translocation of tBID to the mitochondria, which induced the mitochondrial pathway of apoptosis, the knockdown of miR20a also reversed the resistance of TRAIL in established TRAIL-resistant SW480 cells by tBID-mitochondria pathway.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Apoptotic protease-activating factor 1 (APAF1) [6]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HT29 Cells Colon Homo sapiens (Human) CVCL_A8EZ
SW480 cells Colon Homo sapiens (Human) CVCL_0546
FHC cells Colon Homo sapiens (Human) CVCL_3688
Experiment for
Molecule Alteration		 Western blot analysis; Luciferase reporter assay
Experiment for
Drug Resistance		 CCK8 assay; Flow cytometric analysis
Mechanism Description Knockdown of miR27a sensitizes colorectal cancer stem cells to TRAIL by promoting the formation of Apaf-1-caspase-9 complex. miR27a antioligonucleotides enhanced the anti-tumor effect of TRAIL on colorectal cancer stem cells via increasing the expression of Apaf-1.
Key Molecule: BH3-interacting domain death agonist (BID) [7]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Colorectal cancer [ICD-11: 2B91.1]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation TBID/Mitochondria signaling pathway Activation hsa04217
In Vitro Model SW480 cells Colon Homo sapiens (Human) CVCL_0546
NCI-H508 cells Colon Homo sapiens (Human) CVCL_1564
HT-29 cells Colon Homo sapiens (Human) CVCL_0320
SW948 cells Colon Homo sapiens (Human) CVCL_0632
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay; FITC-Annexin V and propidium iodide (PI) assay
Mechanism Description The knockdown of miR20a inhibited the translocation of tBID to the mitochondria, which induced the mitochondrial pathway of apoptosis, the knockdown of miR20a also reversed the resistance of TRAIL in established TRAIL-resistant SW480 cells by tBID-mitochondria pathway.
Pancreatic cancer [ICD-11: 2C10]
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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: HOX transcript antisense RNA (HOTAIR) [3]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Pancreatic cancer [ICD-11: 2C10.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model BxPC-3 cells Pancreas Homo sapiens (Human) CVCL_0186
MIA PaCa-2 cells Pancreas Homo sapiens (Human) CVCL_0428
PANC-1 cells Pancreas Homo sapiens (Human) CVCL_0480
Suit2 cells Pancreas Homo sapiens (Human) CVCL_3172
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Flow cytometric analysis
Mechanism Description The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand.
Liver cancer [ICD-11: 2C12]
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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-942 [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HLCZ01 cells Hepatoma Homo sapiens (Human) CVCL_1J92
LH86 cells Hepatoma Homo sapiens (Human) CVCL_8889
HLCZ02 cells Liver Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interferon alpha-inducible protein 27 (IFI27) [1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
HLCZ01 cells Hepatoma Homo sapiens (Human) CVCL_1J92
LH86 cells Hepatoma Homo sapiens (Human) CVCL_8889
HLCZ02 cells Liver Homo sapiens (Human) N.A.
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-138 [8]
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
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
HLCZ01 cells Hepatoma Homo sapiens (Human) CVCL_1J92
LH86 cells Hepatoma Homo sapiens (Human) CVCL_8889
Experiment for
Molecule Alteration		 RT-qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description microRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Ubiquitin-like protein ISG15 (ISG15) [8]
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
In Vitro Model Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
SMMC7721 cells Uterus Homo sapiens (Human) CVCL_0534
HLCZ01 cells Hepatoma Homo sapiens (Human) CVCL_1J92
LH86 cells Hepatoma Homo sapiens (Human) CVCL_8889
Experiment for
Molecule Alteration		 Western blot analysis; RT-qPCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description microRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells.
Lung cancer [ICD-11: 2C25]
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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-221 [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
TRAIL signaling pathway Inhibition hsa04210
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
H460 cells Lung Homo sapiens (Human) CVCL_0459
Calu1 cells Lung Homo sapiens (Human) CVCL_0608
Experiment for
Molecule Alteration		 qRT-PCR; Northern blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description H460-sensitive cells treated with -221 and -222 pre-miRs become resistant to TRAIL. miR-221 and -222 target the 3'-UTR of kit and p27kip1 mRNAs, but interfere with TRAIL signaling mainly through p27kip1. miR-221 and -222 modulate TRAIL sensitivity in lung cancer cells mainly by modulating p27kip1 expression and TRAIL-induced caspase machinery.
Key Molecule: hsa-mir-222 [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
TRAIL signaling pathway Inhibition hsa04210
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
H460 cells Lung Homo sapiens (Human) CVCL_0459
Calu1 cells Lung Homo sapiens (Human) CVCL_0608
Experiment for
Molecule Alteration		 qRT-PCR; Northern blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description H460-sensitive cells treated with -221 and -222 pre-miRs become resistant to TRAIL. miR-221 and -222 target the 3'-UTR of kit and p27kip1 mRNAs, but interfere with TRAIL signaling mainly through p27kip1. miR-221 and -222 modulate TRAIL sensitivity in lung cancer cells mainly by modulating p27kip1 expression and TRAIL-induced caspase machinery.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Mast/stem cell growth factor receptor Kit (KIT) [2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
TRAIL signaling pathway Inhibition hsa04210
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
H460 cells Lung Homo sapiens (Human) CVCL_0459
Calu1 cells Lung Homo sapiens (Human) CVCL_0608
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description H460-sensitive cells treated with -221 and -222 pre-miRs become resistant to TRAIL. miR-221 and -222 target the 3'-UTR of kit and p27kip1 mRNAs, but interfere with TRAIL signaling mainly through p27kip1. miR-221 and -222 modulate TRAIL sensitivity in lung cancer cells mainly by modulating p27kip1 expression and TRAIL-induced caspase machinery.
Key Molecule: Cyclin-dependent kinase inhibitor 1B (CDKN1B) [2]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
TRAIL signaling pathway Inhibition hsa04210
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
H460 cells Lung Homo sapiens (Human) CVCL_0459
Calu1 cells Lung Homo sapiens (Human) CVCL_0608
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description H460-sensitive cells treated with -221 and -222 pre-miRs become resistant to TRAIL. miR-221 and -222 target the 3'-UTR of kit and p27kip1 mRNAs, but interfere with TRAIL signaling mainly through p27kip1. miR-221 and -222 modulate TRAIL sensitivity in lung cancer cells mainly by modulating p27kip1 expression and TRAIL-induced caspase machinery.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-130a [9]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell migration Activation hsa04670
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
H1299 cells Lung Homo sapiens (Human) CVCL_0060
A459 cells Lung Homo sapiens (Human) CVCL_0023
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in NSCLC cells through the c-Jun mediated downregulation of miR-221 and miR-222.
Key Molecule: hsa-mir-122 [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model H460 cells Lung Homo sapiens (Human) CVCL_0459
Calu1 cells Lung Homo sapiens (Human) CVCL_0608
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 Annexin V staining assay
Mechanism Description PED/PEA-15 has a broad antiapoptotic action, being able to inhibit both the intrinsic and the extrinsic apoptotic pathways. miR-212 negatively modulates PED/PEA-15 expression and sensitizes non-small cell lung cancer (NSCLC) cells to TRAIL-induced apoptosis.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Hepatocyte growth factor receptor (MET) [9]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
PI3K/AKT signaling pathway Inhibition hsa04151
In Vitro Model A549 cells Lung Homo sapiens (Human) CVCL_0023
H1299 cells Lung Homo sapiens (Human) CVCL_0060
A459 cells Lung Homo sapiens (Human) CVCL_0023
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-130a, expressed at low level in lung cancer cell lines, by targeting MET was able to reduce TRAIL resistance in NSCLC cells through the c-Jun mediated downregulation of miR-221 and miR-222.
Key Molecule: Astrocytic phosphoprotein PEA-15 (PEA15) [10]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Non-small cell lung cancer [ICD-11: 2C25.Y]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
In Vitro Model H460 cells Lung Homo sapiens (Human) CVCL_0459
Calu1 cells Lung Homo sapiens (Human) CVCL_0608
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Annexin V staining assay
Mechanism Description PED/PEA-15 has a broad antiapoptotic action, being able to inhibit both the intrinsic and the extrinsic apoptotic pathways. miR-212 negatively modulates PED/PEA-15 expression and sensitizes non-small cell lung cancer (NSCLC) cells to TRAIL-induced apoptosis.
Cervical cancer [ICD-11: 2C77]
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-942 [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Human papillomavirus-related endocervical adenocarcinoma [ICD-11: 2C77.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
In Vitro Model BGC-823 cells Gastric Homo sapiens (Human) CVCL_3360
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Interferon alpha-inducible protein 27 (IFI27) [1]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Human papillomavirus-related endocervical adenocarcinoma [ICD-11: 2C77.2]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell invasion Activation hsa05200
In Vitro Model BGC-823 cells Gastric Homo sapiens (Human) CVCL_3360
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description miR-942 is upregulated in TRAIL-resistant cancer cells and decreased in TRAIL-sensitive ones. miR-942 is inversely correlated with ISG12a expression in cancer tissues and cells. AkT control TRAIL resistance of cancer cells through downregulation of ISG12a by miR-942. Down-regulation of ISG12a by miR-942 is needed to maintain the TRAIL-resistant phenotype.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-126 [11]
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
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
Siha cells Cervix uteri Homo sapiens (Human) CVCL_0032
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR126 reverses drug resistance to TRAIL through inhibiting the expression of c-FLIP in cervical cancer miR126 promotes TRAIL-induced apoptosis in TRAIL-resistant cervical cancer cells and increases the sensitivity of Hela-TR and SiHa-TR to TNF-alphaand FasL.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: CASP8 and FADD-like apoptosis regulator (CFLAR) [11]
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
In Vitro Model Hela cells Cervix uteri Homo sapiens (Human) CVCL_0030
Siha cells Cervix uteri Homo sapiens (Human) CVCL_0032
Experiment for
Molecule Alteration		 Western blot analysis; Luciferase reporter assay
Experiment for
Drug Resistance		 CCK8 assay
Mechanism Description miR126 reverses drug resistance to TRAIL through inhibiting the expression of c-FLIP in cervical cancer miR126 promotes TRAIL-induced apoptosis in TRAIL-resistant cervical cancer cells and increases the sensitivity of Hela-TR and SiHa-TR to TNF-alphaand FasL.
References
Ref 1 miR-942 decreases TRAIL-induced apoptosis through ISG12a downregulation and is regulated by AKT. Oncotarget. 2014 Jul 15;5(13):4959-71. doi: 10.18632/oncotarget.2067.
Ref 2 MicroRNA signatures of TRAIL resistance in human non-small cell lung cancer. Oncogene. 2008 Jun 19;27(27):3845-55. doi: 10.1038/onc.2008.6. Epub 2008 Feb 4.
Ref 3 The long non-coding RNA HOTAIR enhances pancreatic cancer resistance to TNF-related apoptosis-inducing ligand. J Biol Chem. 2017 Jun 23;292(25):10390-10397. doi: 10.1074/jbc.M117.786830. Epub 2017 May 5.
Ref 4 MiR-424 and miR-27a increase TRAIL sensitivity of acute myeloid leukemia by targeting PLAG1. Oncotarget. 2016 May 3;7(18):25276-90. doi: 10.18632/oncotarget.8252.
Ref 5 miR-494 Sensitizes Gastric Cancer Cells to TRAIL Treatment Through Downregulation of Survivin. Cell Physiol Biochem. 2018;51(5):2212-2223. doi: 10.1159/000495867. Epub 2018 Dec 7.
Ref 6 Knockdown of miR-27a sensitizes colorectal cancer stem cells to TRAIL by promoting the formation of Apaf-1-caspase-9 complex. Oncotarget. 2017 Jul 11;8(28):45213-45223. doi: 10.18632/oncotarget.16779.
Ref 7 miR-20a-directed regulation of BID is associated with the TRAIL sensitivity in colorectal cancer. Oncol Rep. 2017 Jan;37(1):571-578. doi: 10.3892/or.2016.5278. Epub 2016 Nov 28.
Ref 8 MicroRNA-138 enhances TRAIL-induced apoptosis through interferon-stimulated gene 15 downregulation in hepatocellular carcinoma cells. Tumour Biol. 2017 Jun;39(6):1010428317710410. doi: 10.1177/1010428317710410.
Ref 9 miR-130a targets MET and induces TRAIL-sensitivity in NSCLC by downregulating miR-221 and 222. Oncogene. 2012 Feb 2;31(5):634-42. doi: 10.1038/onc.2011.260. Epub 2011 Jun 27.
Ref 10 miR-212 increases tumor necrosis factor-related apoptosis-inducing ligand sensitivity in non-small cell lung cancer by targeting the antiapoptotic protein PED. Cancer Res. 2010 May 1;70(9):3638-46. doi: 10.1158/0008-5472.CAN-09-3341. Epub 2010 Apr 13.
Ref 11 MiR-126 reverses drug resistance to TRAIL through inhibiting the expression of c-FLIP in cervical cancer. Gene. 2017 Sep 5;627:420-427. doi: 10.1016/j.gene.2017.06.055. Epub 2017 Jun 29.

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