Aberrant expression of enzymes regulating m6A mRNA methylation: implication in cancer

Natalia Pinello, et al.

Abstract


N6-methyladenosine (m6A) is an essential RNA modification that regulates key cellular processes, including stem cell renewal,cellular differentiation, and response to DNA damage. Unsurprisingly, aberrant m6A methylation has been implicated in thedevelopment and maintenance of diverse human cancers. Altered m6A levels affect RNA processing, mRNA degradation, andtranslation of mRNAs into proteins, thereby disrupting gene expression regulation and promoting tumorigenesis. Recent studieshave reported that the abnormal expression of m6A regulatory enzymes affects m6A abundance and consequently dysregulates theexpression of tumor suppressor genes and oncogenes, including MYC, SOCS2, ADAM19, and PTEN. In this review, we discuss thespecific roles of m6A “writers", “erasers”, and “readers” in normal physiology and how their altered expression promotestumorigenesis. We also describe the potential of exploiting the aberrant expression of these enzymes for cancer diagnosis,prognosis, and the development of novel therapies.

Keywords


RNA modification; N6-methyladenosine (m6A); cancer; tumor suppressor; oncogene

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