Table 2 miRNAs reported to regulate other mediators of drug resistance
Target gene | Biological effect of target gene | MicroRNA | Validation of miRNA binding site | Prediction by miRNA database(s) | Identification method | Cancer type/Significance/Specific type of drug resistance | Study in patient samples? | Reference |
|---|---|---|---|---|---|---|---|---|
BAX | Pro-apoptotic | miR-296↑ | Luciferase reporter assay + miRNA antagomir | -- | miRNA microarray profiling | Esophageal squamous cell carcinoma | Yes | [26] |
BCL2 | Anti-apoptotic | miR-15b↓ | Luciferase reporter assay + site-driected mutagenesis of Bcl-2 3′UTR + miRNA mimic | miRBase & TargetScan | miRNA microarray profiling | Gastric | No | [19] |
miR-16↓ | ||||||||
BCL2 | Anti-apoptotic | miR-1915↓ | Luciferase reporter assay + site-directed mutagenesis of Bcl-2 3′UTR + miRNA mimics & inhibitors | miRDB; TargetScan (4 possible miRNA binding sites within Bcl-2 3′UTR) | miRNA microarray profiling | Colorectal | No | [40] |
BCL2 & SIRT1 | Anti-apoptotic | miR-34a↓ | Direct miRNA effect (on Bcl-2 & SIRT1 mRNA): Luciferase reporter +/- miRNA mimic | TargetScan | Mechanistic investigation of miR-34a/Bcl-2 and miR-34a/SIRT1 pathways in taxane-based chemotherapy | Prostate / Paclitaxel resistance | No | [41] |
Indirect miRNA effect (through HuR): Gene expression analysis +/- miRNA mimic | ||||||||
BMI-1 | PcGa protein – transcriptional repressor | miR-200c↓ | Gene expression analysis after infection with miR-200c vector | -- | miRNA microarray analysis | Melanoma /miR-200c is commonly found to be downregulated in malignant melanoma that possess self-renewal cancer stem-cell like property and are more invasive. The prominent miR-200c downregulation is accompanied by Bmi-1 overexpression, which was found to cause loss of E-cadherin (thereby EMT) and overexpression of MDR transporters (including ABCG2, ABCG5 and MDR). | Yes | [42] |
CDH1 | EMTb transition | mR-200c↓ | Indirect regulation: The two miRNAs repress ZEB1 & ZEB2, thereby leading to loss of E-cadherin and a EMT phenotype | -- | Mechanistic investigation of the role of miRNAs in EMT-linked docetaxel resistance in prostate cancer | Prostate/Docetaxel resistance/Docetaxel treatment triggers EMT to inhibit apoptosis through the proposed miR-200c/205/ZEB1/ZEB2/E-cadherin pathway | No | [43] |
miR-205↓ | ||||||||
DHFR | Folate metabolism | miR-24 (DHFR SNP 829C > T makes DHFR mRNA indifferent to miR-24) | Gene expression analysis + Site-directed mutagenesis + miRNA mimics & inhibitors | MiRanda & miRBase | A 829C > T SNP identified in DHFR gene in Japanese population was found to be associated with increased DHFR message | Fibrosarcoma/methotrexate resistance | No | [20] |
HIPK2 | Tumor suppressor | miR-27a↑ | NO attempt to verify binding of miR-27a on HIPK2 3′UTR | TargetScan | Identified during the study of indirect effect of miR-27a on MDR-1 expression | Ovarian | No | [23] |
PTEN | Tumor suppressor | miR-214↑ | Luciferase reporter assay + site-driected mutagenesis of PTEN 3′UTR + miRNA mimic | -- | miRNA microarray profiling | Ovarian/cisplatin resistance | Yes | [21] |
TUBB3 | Structural protein (β-tubulin) | miR-200c↓ | Gene expression analysis +/- miRNA mimic | -- | miRNA microarray profiling | Resistance to microtubule –binding chemotherapeutic drugs | No | [44] |