Novel insights into mutual regulation between N6-methyladenosine modification and LncRNAs in tumors

Abstract

N6-methyladenosine (m6A), one of the most common RNA methylation modifications, has emerged in recent years as a new layer of the regulatory mechanism controlling gene expression in eukaryotes. As a reversible epigenetic modification, m6A not only occurs on mRNAs but also on Long non-coding RNAs (LncRNAs). As we all known, despite LncRNAs cannot encode proteins, they affect the expression of proteins by interacting with mRNAs or miRNAs, thus playing important roles in the occurrence and development of a variety of tumors. Up to now, it has been widely accepted that m6A modification on LncRNAs affects the fate of the corresponding LncRNAs. Interestingly, levels and functions of m6A modifications are also mediated by LncRNAs through affecting the m6A methyltransferases (METTL3, METTL14, WTAP, METTL16, etc.), demethylases (FTO, ALKBH5) and methyl-binding proteins (YTHDFs, YTHDCs, IGF2BPs, HNRNPs, etc.), which are collectively referred to as “m6A regulators”. In this review, we summarized the mutual regulation mechanisms between N6-methyladenosine modification and LncRNAs in cancer progression, metastasis, invasion and drug resistance. In detail, we focus on the specific mechanisms of m6A modification, which is mediated by methyltransferases and demethylases, involves in the regulation of LncRNA levels and functions in the first part. And section two intensively displays the mediation roles of LncRNAs in m6A modification via changing the regulatory proteins. At last part, we described the interaction effects between LncRNAs and methyl-binding proteins of m6A modification during various tumor occurrence and development.

N6-Methyladenosine in Cell-Fate Determination of BMSCs: From Mechanism to Applications

“…In addition to directly regulating the expression of mRNAs, m 6 A modification of ncRNAs, especially lncRNAs and miRNAs, has garnered growing interest in recent years, although the number of related studies is much lower (Fig. 1 ) [ 14 , 16 ]. NcRNAs and m 6 A may cooperate or compete to jointly regulate target mRNAs [ 14 , 16 ].…”

“…1 ) [ 14 , 16 ]. NcRNAs and m 6 A may cooperate or compete to jointly regulate target mRNAs [ 14 , 16 ]. Moreover, previous studies have suggested that ncRNAs are the main sites of RNA epigenetic modification [ 17 ].…”

New insights into the interaction between m6A modification and lncRNA in cancer drug resistance

“…These studies aimed to understand the influence of m6A modification on various aspects such as transcript localization, splicing, turnover and translation rates. 42 Nowadays, the use of transcriptome‐wide mapping techniques has led to the identification of a significant number of m6A‐modified lncRNA. Subsequent studies have demonstrated that these m6A‐modified lncRNA plays vital roles in nucleus, cytoplasm, and extracellular environment.…”

Negative Regulation of LINC01013 by METTL3 and YTHDF2 Enhances the Osteogenic Differentiation of Senescent Pre‐Osteoblast Cells Induced by Hydrogen Peroxide

“…The most common internal RNA modification in eukaryotes is the N6‐methyladenosine (m6A) methylation, which appears in microRNAs, ribosomal RNAs, circular RNAs, and especially lncRNAs. [ 23 ] The biological functions of m6A modifications are controlled by m6A regulators, including m6A methyltransferases (m6A writers), m6A demethylases (m6A erasers), and m6A‐binding proteins (m6A readers). [ 24 ] METTL3 is a crucial component of the m6A writer complex and contributes significantly to the regulation of m6A methylation levels, impacting cell survival, stem cell maintenance, and cell fate decisions.…”