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Table 2 miRNAs reported to regulate other mediators of drug resistance

From: MicroRNA: a prognostic biomarker and a possible druggable target for circumventing multidrug resistance in cancer chemotherapy

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]
  1. a PcG = polycomb group protein (transcriptional repressor).
  2. b EMT = epithelial-to-mesenchymal transition.