Mutual regulation between N6-methyladenosine (m6A) modification and circular RNAs in cancer: impacts on therapeutic resistance

Abstract

The resistance of tumor cells to therapy severely impairs the efficacy of treatment, leading to recurrence and metastasis of various cancers. Clarifying the underlying mechanisms of therapeutic resistance may provide new strategies for overcoming cancer resistance. N6-methyladenosine (m6A) is the most prevalent RNA modification in eukaryotes, and is involved in the regulation of RNA splicing, translation, transport, degradation, stability and processing, thus affecting several physiological processes and cancer progression. As a novel type of multifunctional non-coding RNAs (ncRNAs), circular RNAs (circRNAs) have been demonstrated to play vital roles in anticancer therapy. Currently, accumulating studies have revealed the mutual regulation of m6A modification and circRNAs, and their interaction can further influence the sensitivity of cancer treatment. In this review, we mainly summarized the recent advances of m6A modification and circRNAs in the modulation of cancer therapeutic resistance, as well as their interplay and potential mechanisms, providing promising insights and future directions in reversal of therapeutic resistance in cancer.

Novel insights into the multifaceted roles of m6A-modified LncRNAs in cancers: biological functions and therapeutic applications

“…Due to the rapid multiplication rate, it is easy for cancer cells to form drug resistance to therapy, which severely weakens the efficacy of treatment. Clarifying the mechanism of how cancer cells form drug resistance can be urgent and valuable for cancer treatment [ 100 ].…”

The regulatory roles of circular RNAs via autophagy in ischemic stroke

“…Due to different splicing processes, circRNAs were divided into three main types, including exonic circRNAs (ecircRNAs), exon-intron circRNAs (EIciRNAs), and circular intronic RNAs (ciRNAs) ( 59 ). However, with advances in experimental technology, emerging evidence has indicated that circRNAs are implicated in the occurrence and development of many diseases, such as cancer ( 60 ), cardiovascular disorders ( 61 ), neurological disorders ( 62 ), metabolic disorders ( 63 ), and immunological disorders ( 64 ). The functions of circRNAs are as follows: acting as a sponge of miRNA or competitive endogenous RNAs (ceRNAs), interacting with RNA-binding proteins (RBPs) and mRNAs, regulating transcription or alternative splicing, and protein translation ( 65 ).…”

N6-methyladenosine (m6A) reader IGF2BP1 facilitates clear-cell renal cell carcinoma aerobic glycolysis

“…N 6 -methyladenosine (m 6 A) modification is firstly described in 1971 years, which has shown critical roles in mRNA metabolism and become focus recently ( Chen et al, 2022 ; Li et al, 2022 ). Methyltransferase installed the m 6 A modification on mRNA, including methyltransferase-like 3 (METTL3), methyltransferase-like 14 (METTL14), and the Wilms tumor 1-associated protein (WTAP) ( Lin et al, 2022 ; Luo et al, 2022 ). In addition, the m 6 A modification was wiped by demethylase, including obesity-associated protein (FTO) and alkB homolog 5 (ALKBH5) ( Qin et al, 2022 ; Zhai et al, 2022 ).…”