Targeting non-coding RNAs to overcome cancer therapy resistance

Abstract

It is now well known that non-coding RNAs (ncRNAs), rather than protein-coding transcripts, are the preponderant RNA transcripts. NcRNAs, particularly microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), are widely appreciated as pervasive regulators of multiple cancer hallmarks such as proliferation, apoptosis, invasion, metastasis, and genomic instability. Despite recent discoveries in cancer therapy, resistance to chemotherapy, radiotherapy, targeted therapy, and immunotherapy continue to be a major setback. Recent studies have shown that ncRNAs also play a major role in resistance to different cancer therapies by rewiring essential signaling pathways. In this review, we present the intricate mechanisms through which dysregulated ncRNAs control resistance to the four major types of cancer therapies. We will focus on the current clinical implications of ncRNAs as biomarkers to predict treatment response (intrinsic resistance) and to detect resistance to therapy after the start of treatment (acquired resistance). Furthermore, we will present the potential of targeting ncRNA to overcome cancer treatment resistance, and we will discuss the challenges of ncRNA-targeted therapy—especially the development of delivery systems.

CircEZH2/miR-133b/IGF2BP2 aggravates colorectal cancer progression via enhancing the stability of m6A-modified CREB1 mRNA

“…Based on accumulating evidence, circRNAs are implicated in the development of human diseases, including diabetes, neurological disorders, cardiovascular diseases, and especially cancers [ 10 – 13 ]. In recent years, circRNAs are emerging as critical regulators in carcinogenesis and cancer progression by competitively sponging regulatory miRNAs or interacting with RNA-binding proteins [ 14 , 15 ]. In CRC, circRNAs are aberrantly expressed and exert important effects on tumorigenesis and cancer progression [ 16 ].…”

miR‑let‑7c‑3p targeting on Egr‑1 contributes to the committed differentiation of leukemia cells into monocyte/macrophages

“…Different miRNA species serve different roles in the formation or reversal of drug resistance. It can be used both as a biomarker of drug resistance and as one of the targets for drug resistance intervention (66,67). For example, miRNA expression profiling of drug-resistant melanoma patients and their cell lines reveals that miRNA-181a and miRNA-181b are significantly downregulated in drug-resistant melanoma patients and drug-resistant cell lines.…”

Non-coding RNA in cancer drug resistance: Underlying mechanisms and clinical applications

“…The dysregulation of lncRNAs has been shown to participate in the development of cancer drug resistance through interference with cellular apoptosis or proliferation pathways (18,183). For instance, Li et al revealed that lncRNA TINCR was significantly increased in CDDP-resistant choroidal melanoma (CM) tissues and cells.…”

“…Furthermore, circRNA C190 overexpression facilitated the proliferation, and migration of non-small cell lung carcinoma (NSCLC) cell lines by targeting CDK1 and CDK6 via sequestrating miR-142-5p (17). Notably, ncRNA dysregulation contributes to the development of cancer drug resistance via various mechanisms, such as the inhibition of apoptosis, enhancement of epithelial-to-mesenchymal transition (EMT), and induction of autophagy (18)(19)(20). In addition, the differential expression patterns of ncRNAs endow them with great potential as biomarkers and therapeutic targets for cancer patients.…”