Multifaceted Roles of the N6-Methyladenosine RNA Methyltransferase METTL3 in Cancer and Immune Microenvironment

Biomolecules. 2022 Jul 28;12(8):1042. doi: 10.3390/biom12081042.

Abstract

As the most abundant internal mRNA modification in eukaryotic cells, N6-methyladenosine (m6A) has emerged as an important regulator of gene expression and has a profound impact on cancer initiation and progression. mRNA m6A modification is regulated by m6A methyltransferases, demethylases and reader proteins to fine tune gene expression at the post-transcriptional level. The most well-studied m6A methyltransferase, METTL3, plays critical roles in regulating gene expression and affecting the outcome of various cancers. In this review, we discuss the multifaceted roles of METTL3 in regulating specific molecular signaling pathways in different types of cancers and the recent progress on how METTL3 impacts the tumor immune microenvironment. Finally, we discuss future directions and the potential for therapeutic targeting of METTL3 in cancer treatment.

Keywords: METTL3; RNA modification; m6A; methyltransferase; tumor immune microenvironment.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine / analogs & derivatives
  • Adenosine / metabolism
  • Humans
  • Methyltransferases / genetics
  • Methyltransferases / metabolism*
  • Neoplasms* / genetics
  • RNA, Messenger / genetics
  • Tumor Microenvironment

Substances

  • RNA, Messenger
  • N-methyladenosine
  • Methyltransferases
  • METTL3 protein, human
  • Adenosine

Grants and funding

This study was supported by the Lung Cancer Project from Beijing Municipal Health Commission 2020–2022.