N6-methyladenine RNA modification and cancer

Abstract

N6-methyladenosine (m6A) in messenger RNA (mRNA) is regulated by m6A methyltransferases and demethylases. Modifications of m6A are dynamic and reversible, may regulate gene expression levels and serve vital roles in numerous life processes, such as cell cycle regulation, cell fate decision and cell differentiation. In recent years, m6A modifications have been reported to exhibit functions in human cancers via regulation of RNA stability, microRNA processing, mRNA splicing and mRNA translation, including lung cancer, breast tumor and acute myeloid leukemia. In the present review, the roles of m6A modifications in the onset and progression of cancer were summarized. These modifications display an oncogenic role in certain types of cancer, whereas in other types of cancer they exhibit a tumor suppressor role. Therefore, understanding the biological functions performed by m6A in different types of tumors and identifying pivotal m6A target genes to deduce the potential mechanisms underlying the progression of cancer may assist in the development of novel therapeutics.

Keywords: N6-methyladenosine; RNA modification; cancer; epigenetics; mRNA.

Figure 1.

Mechanism of N6-methyladenine RNA modification. m6A methylation is dynamically and reversibly regulated by methyltransferases (METTL3, METTL14, WTAP, KIAA1429 among others) and demethylases (FTO and ALKBH5). M6A readers (YTHDF1, YTHDF2, YTHDF3, YTHDC1 and YTHDC2) read the m6A-mediated physiological effects and influence RNA behaviors. METTL3, methyltransferase-like 3; METTL14, methyltransferase-like 14; METTL16, methyltransferase-like 16; WTAP, Wilms' tumor 1-associating protein; RBM15, RNA binding motif protein 15; FTO, fat mass and obesity-associated protein; ALKBH5, alkB homolog 5; YTHDF1, YTH domain-containing family protein 1; YTHDF2, YTH domain-containing family protein 2; YTHDF3, YTH domain-containing family protein 3; YTHDC1, YTH domain-containing protein 1; YTHDC2, YTH domain-containing protein 2; eIF3, eukaryotic translation initiation factor 3; IGF2BP, insulin-like growth factor 2 mRNA-binding protein; FMR1, fragile X mental retardation 1; LRPPRC, leucine rich pentatricopeptide repeat containing.