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Table 1 miRNAs reported to regulate MDR transporters to mediate chemoresistance

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

Transporter targets MicroRNA dysregulation Direct binding site(s) on target gene? Prediction by miRNA database(s) Identification method Cancer type Study in patient samples? Reference
ABCB1 miR-27a↑ Indirect regulation-targets HIPK2 (a transcriptional corepressor that inhibits HIF-1αactivity), thereby indirectly activating MDR-1/P-gp TargetScan suggests that HIPK2 is a possible target for miR-27a Serendipitous testing of miR-27a in the development of drug resistance in ovarian cancer cell lines Ovarian No [23]
miR-27a↑, miR-451↑ Likely indirect regulation -- miRNA microarray profiling Ovarian No [24]
(i.e. not via ABCB1 3′UTR)
miR-27a & miR-451 mimics elevate ABCB1 mRNA
miR-122↓ NO attempt to verify binding of miR-122 on MDR-1 3′UTR NOT performed Serendipitous testing of downregulation of MDR related genes (MDR-1, MRP & GST-π) by miR-122 Hepatocellular carcinoma No [25]
miR-296↑ Likely indirect regulation -- miRNA microarray profiling Esophageal squamous cell carcinoma Yes [26]
(i.e. not via ABCB1 3′UTR)
- antagomir of miR-296 decrease ABCB1 promoter activity
miR-298↓ Confirmed by luciferase reporter assay / MDR-1 3′UTR miRNA site deletion / miRNA mimic / miRNA inhibitor miRanda miRNA microarray Breast cancer No [27]
miR-1253↓
let-7 g↓ Indirect regulation    Ovarian Yes [28]
• targets IMP-1 (a RNA-binding protein)
• IMP-1 is known to stabilize MDR1 mRNA
• loss of let-7 g commonly observed in various cancers could therefore allow overexpression of IMP-1 and stability of MDR-1/P-gp to mediate drug resistance
ABCC1 miR-326↓ Confirmed by luciferase reporter assay / ABCC1 3′UTR miRNA site deletion / gene expression analysis after transfection with miR-326 mimic TargetScan miRNA microarray profiling Breast cell line + early/advanced breast cancer tissue Yes [29]
miR-1291↓ Confirmed by luciferase reporter/miRNA mimic/miRNA inhibitor RNAhybrid, TargetScan, miRanda, PITA Serendipitous study of the role of SNORA34 to generate miR-1291, which subsequently controls chemosensitivity Pancreatic No [30]
ABCC2 miR-297↓ Luciferase reporter/miRNA mimic/miRNA inhibitor TargetScan miRNA microarray profiling Colorectal Yes [31]
ABCC3 & ABCC6 miR-9*↓ Indirect regulation PicTar, TargetScan, miRBase, miRanda Serendipitous study of the role of ID4 in chemoresistance of induced glioma stem cells Glioma Yes [32]
• miR-9* is a SOX2-targeting miRNA
• novel ID4-miR-9*-SOX2-ABCC3/ABCC6 regulatory pathway
• ID4 was found to confer chemoresistance to glioma stem cells by inducing the expression of two SOX2-mediated ABC transporters (ABCC3 & ABCC6) through suppression of miR-9*
ABCG2 miR-212↓, miR-328↓ Effect of miR-212 & miR-328 on ABCG2 expression was evaluated by gene expression analysis and luciferase reporter gene assay -- miRNA microarray profiling in imatinib-selected K562 cells Leukemia (short-term /long-term imatinib treatmet) No [33]
miR-328↓ Confirmed by luciferase reporter assay / ABCG2 3′UTR miRNA site deletion / miRNA mimic / miRNA antagomir PITA; TargetScan Bioinformatic analysis Breast No [18]
miR-328↓ Confirmed by luciferase reporter assay / gene expression analysis after transfection with miRNA mimic or inhibitor -- miRNA microarray analysis on SP# vs non-SP# cells Colorectal cell lines + primary biopsies Yes [34]
miR-328↓, miR-519c↓, miR-520 h↓ Confirmed by luciferase reporter assay with site-directed gene mutagenesis / gene expression analysis after transfection with miRNA mimics TargetScan, PITA, MicroCosm Targets, RNA22 Bioinformatic analysis Breast, Stem-like cells from human retinoblastoma No [35]
miR-519c (shortening of ABCG2 3′UTR escape miR-519c repression) Confirmed by luciferase reporter assay with site-directed gene mutagensis on ABCG2 3′UTR miRNA site / gene expression analysis after transfection with miRNA mimics or inhibitor miRBase TARGETS, RNAHybrid, UTRScan program Bioinformatic analysis Colon No [16, 17]
miR-520 h↓ Confirmed by luciferase reporter assay +/- miRNA mimic & inhibitor PicTar, miRanda, TargetScan miRNA microarray profiling of CD34+ hematopoietic cells Leukemia No [36]
miR-520 h↓ Confirmed by gene expression analysis after miRNA mimic transfection miRanda, TargetScan, TarBase Bioinformatic analysis Pancreatic No [37]
miR-181a↓ Confirmed by luciferase reporter assay and gene expression analysis +/- miRNA mimic & inhibitor RNAhybrid miRNA microarray analysis to compare sensitive and resistant cells Breast No [38]
  miR-487a↓ Confirmed by luciferase reporter assay and gene expression analysis +/- miRNA mimic & inhibitor Confirmed by luciferase reporter assay and gene expression analysis +/- miRNA mimic & inhibitor TargetScan, PITA, RNAhybrid Bioinformatic analysis Breast No [39]
  1. # SP = side population; Non-SP = non-side population.