RNA N6-methyladenosine modification in solid tumors: new therapeutic frontiers.

Epigenetic mRNA modification is an evolving field. N6-methyladenosine (m6A) is the most frequent internal transcriptional modification in eukaryotic messenger RNAs (mRNAs). This review will discuss the functions of the m6A mRNA machinery, including its "writers" that are components of the methyltransferase complex, its "readers" and its "erasers" (specifically FTO and ALKBH5) in cancer. The writers deposit the m6A and include METTL3, METTL14, WTAP, VIRMA, and RBM15. M6A methylation is removed by the m6A demethylases (FTO and ALKBH5). Lastly, the most diverse members are the readers that can contribute to mRNA splicing, stability, translation, and nuclear export. Many of these functions continue to be elucidated. The dysregulation of this machinery in various malignancies and the associated impact on tumorigenesis and drug response will be discussed herein with a focus on solid tumors. It is clear that, by contributing to either mRNA stability or translation, there are downstream targets that are impacted, contributing to cancer progression and the self-renewal ability of cancer stem cells.