Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential

Abstract

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract, with the annual incidence and mortality increasing consistently. Oxaliplatin-based chemotherapy is a preferred therapeutic regimen for patients with advanced CRC. However, most patients will inevitably develop resistance to oxaliplatin. Many studies have reported that non-coding RNAs (ncRNAs), such as microRNAs, long non-coding RNAs, and circular RNAs, are extensively involved in cancer progression. Moreover, emerging evidence has revealed that ncRNAs mediate chemoresistance to oxaliplatin by transcriptional and post-transcriptional regulation, and by epigenetic modification. In this review, we summarize the mechanisms by which ncRNAs regulate the initiation and development of CRC chemoresistance to oxaliplatin. Furthermore, we investigate the clinical application of ncRNAs as promising biomarkers for liquid CRC biopsy. This review provides new insights into overcoming oxaliplatin resistance in CRC by targeting ncRNAs.

Keywords: Colorectal cancer; Liquid biopsy biomarkers; Non-coding RNAs; Oxaliplatin; Resistance.

Figure 1

Classification of non-coding RNAs. Non-coding RNAs can be divided into either small ncRNAs (< 200 nucleotides) or long non-coding RNAs (> 200 nucleotides) based on their length. Among these, small ncRNAs consist of ribosomal RNAs, transfer RNAs, small nucleosome/spliced RNAs, microRNAs, small interfering RNAs, PiWI-Interacting RNAs, and small nucleolar RNAs. Furthermore, the circular RNAs generated in the splicing process of pre-mRNA are also considered to be special ncRNAs. ncRNAs: Non-coding RNAs; lncRNAs: Long non-coding RNAs; rRNAs: Ribosomal RNAs; tRNAs: Transfer RNAs; snRNAs: Small nucleosome/spliced RNAs; miRNAs; MicroRNAs; siRNAs: Small interfering RNAs; piRNAs: PiWI-Interacting RNAs; snoRNAs: Small nucleolar RNAs.

Figure 2

Overview of the mechanisms by which several non-coding RNAs exert oxaliplatin resistance in colorectal cancer. Various microRNAs, long non-coding RNAs, and circular RNAs are up-regulated or down-regulated in colorectal cancer and mediate oxaliplatin resistance via a multitude of mechanisms. These mechanisms include acting as competing endogenous RNAs, generating encoded peptides, regulating autophagy, inducing apoptosis, and interfering with DNA damage and repair. In particular, several non-coding RNAs have been demonstrated to confer oxaliplatin resistance in colorectal cancer cells via exosomes. CRC: Colorectal cancer; lncRNAs: Long non-coding RNAs; miRNAs; MicroRNAs; circRNAs: Circular RNAs.