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.

Keywords: Demethylases; LncRNAs; Methyl-binding proteins; Methyltransferases; N6-methyladenosine.