The role of non-coding RNAs in ABC transporters regulation and their clinical implications of multidrug resistance in cancer

Multi-drug resistance (MDR) is a hindrance toward the successful treatment of cancers. The primary mechanism that gives rise to acquired chemoresistance is the overexpression of adenosine triphosphate-binding cassette (ABC) transporters. The dysregulation of non-coding RNAs (ncRNAs) is a widely concerned reason contributing to this phenotype.In this review, we describe the role of intracellular and exosomal ncRNAs including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) in ABC transporters-induced tumor MDR. Meanwhile, we will introduce the potential therapeutic strategies which reverse MDR in terms of reducing the expression of ABC transporters via targeting ncRNAs, like nucleic acid delivery with nanoparticles as well as miRNAs-targeted small molecular compounds.The dysregulated ncRNAs-mediated overexpression of ABC transporters in chemo-resistant cancer is not negligible. Finding out the underlying mechanism may provide a theoretical basis for clinical therapy of cancer MDR, and the emergence of new approaches for gene therapy targeting ncRNAs to suppress ABC transporters makes reversing cancer MDR possible despite its clinical application requires further investigations. Also, the discovered ncRNAs regulating ABC transporters in chemo-resistant cancers are just a tip of the iceberg of the genetic transcripts, especially for circRNAs, which justify more concern.Abbreviations: MDR, multi-drug resistance; ABC, adenosine triphosphate-binding cassette; NcRNAs, non-coding RNAs; MiRNAs, microRNAs; LncRNAs, long non-coding RNAs; CircRNAs, circular RNAs; CeRNAs, competing endogenous RNAs; 3'UTR, 3'-untranslated regions; SLC, solute carrier; ABCB1/MDR1, ABC subfamily B member 1; ABCG2/BCRP, ABC subfamily G member 2; ABCCs/MRPs, ABC subfamily C 1 to 12; DLL1: Delta-like protein 1; DTX, docetaxel; DOX/ADM/ADR, doxorubicin/adriamycin; PTX, paclitaxel; VBL, vinblastine; VCR, vincristine; MTX, methotrexate; CDDP/DDP, cisplatin/cis-diaminedichloroplatinum; OXA/L-OHP, oxaliplatin; TMZ, temozolomide; 5-FU, 5-fluorouracil; MTA, pemetrexed; NSCLC, non-small cell lung carcinoma; HCC, hepatocellular carcinoma; CRC, colorectal carcinoma; RB, retinoblastoma; RCC, renal cell carcinoma; OS, osteosarcoma; PDAC, pancreatic ductal adenocarcinoma; TNBC, triple-negative breast cancer.