Novel insights into mutual regulation between N(6)-methyladenosine modification and LncRNAs in tumors

N(6)-methyladenosine (m(6)A), 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, m(6)A 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 m(6)A modification on LncRNAs affects the fate of the corresponding LncRNAs. Interestingly, levels and functions of m(6)A modifications are also mediated by LncRNAs through affecting the m(6)A methyltransferases (METTL3, METTL14, WTAP, METTL16, etc.), demethylases (FTO, ALKBH5) and methyl-binding proteins (YTHDFs, YTHDCs, IGF2BPs, HNRNPs, etc.), which are collectively referred to as “m(6)A regulators”. In this review, we summarized the mutual regulation mechanisms between N(6)-methyladenosine modification and LncRNAs in cancer progression, metastasis, invasion and drug resistance. In detail, we focus on the specific mechanisms of m(6)A 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 m(6)A modification via changing the regulatory proteins. At last part, we described the interaction effects between LncRNAs and methyl-binding proteins of m(6)A modification during various tumor occurrence and development.