Emerging role of long non-coding RNAs in cisplatin resistance

Abstract

Cisplatin (CDDP) is one of the most commonly used chemotherapy drugs for the treatment of various cancers. Although platinum-based therapies are highly efficacious against rapidly proliferating malignant tumors, the development of CDDP resistance results in significant relapse as well as decreased overall survival rates, which is a significant obstacle in CDDP-based cancer therapy. Long non-coding RNAs (lncRNAs) are involved in cancer development and progression by the regulation of processes related to chromatin remodeling, transcription, and posttranscriptional processing. Emerging evidence has recently highlighted the roles of lncRNAs in the development of CDDP resistance. In this review, we discuss the roles and mechanisms of lncRNAs in CDDP chemoresistance, including changes in cellular uptake or efflux of a drug, intracellular detoxification, DNA repair, apoptosis, autophagy, cell stemness, and the related signaling pathways, aiming to provide potential lncRNA-targeted strategies for overcoming drug resistance in cancer therapy.

Keywords: cancer; chemoresistance; cisplatin; lncRNAs.

Figure 1

Molecular mechanisms of cisplatin resistance. Notes: Multiple cellular alterations in cancer cells, including cell cycle, apoptosis, autophagy, stemness, intracellular detoxification, and drug influx/efflux, contribute to cisplatin chemoresistance through genetic and/or epigenetic regulation of multiple signaling pathways. Some major genetic and epigenetic factors are illustrated in the figure (see text for detailed discussion). Abbreviations: ALDH1, aldehyde dehydrogenase 1 family member A1; ATG7, autophagy associated gene; BRCA2, breast cancer susceptibility proteins 2; CTR1, copper transporter 1; ERCC1, excision repair cross-complementing rodent repair deficiency, complementation group 1; GSH, glutathione; GST, glutathione S-transferase; HR, homologous recombination; MMR, mismatch repair; MRP, multidrug-resistant-associated protein; NER, nucleotide excision repair; γ-GCS, γ-glutamylcysteine synthetase.

Figure 2

Role of lncRNAs in cisplatin resistance. Notes: lncRNAs that regulate drug efflux, drug uptake, apoptosis, DDR, cell cycle arrest, and autophagy of cancer cells are implicated in cisplatin resistance. Gray arrows indicate inhibition and black arrows indicate activation. Abbreviations: DDR, DNA damage response; lncRNAs, long non-coding RNAs; MDR1, multidrug-resistant protein; MRP1, multidrug-resistant-associated protein 1.