Function of N6-Methyladenosine Modification in Tumors

Abstract

N6-Methyladenosine (m6A) modification is a dynamic and reversible methylation modification at the N6-position of adenosine. As one of the most prevalent posttranscriptional methylation modifications of RNA, m6A modification participates in several mRNA processes, including nuclear export, splicing, translation, and degradation. Some proteins, such as METTL3, METTL14, WTAP, ALKBH5, FTO, and YTHDF1/2/3, are involved in methylation. These proteins are subdivided into writers (METTL3, METTL14, WTAP), erasers (ALKBH5, FTO), and readers (YTHDF1/2/3) according to their functions in m6A modification. Several studies have shown that abnormal m6A modification occurs in tumors, including colorectal cancer, liver cancer, breast cancer, nasopharyngeal carcinoma, and gastric cancer. The proteins for m6A modification are involved in tumor proliferation, angiogenesis, metastasis, immunity, and other processes. Herein, the roles of m6A modification in cancer are discussed, which will improve the understanding of tumorigenesis, as well as the diagnosis, treatment, and prognosis of tumors.

N6-methyladenosine (m6A) methyltransferase METTL3-mediated LINC00680 accelerates osteoarthritis through m6A/SIRT1 manner

“…Emerging evidence indicates that m 6 A modification participates in the human pathophysiological process [ 22 , 23 ]. As an indispensable form of epigenetic modification, m 6 A is suggested as an essential regulator regarding bone disease.…”

Role of m6A modification in female infertility and reproductive system diseases

“…For example, YTHDF1 promotes the translation of m6A modified mRNA, while YTHDF2 lowers mRNA stability, induces mRNA degradation, and mediates mRNA subcellular localization and selective splicing. (Figure 1) The other types of m6A protein machineries have been introduced in detail in a large number of reviews [19,20].…”

Functions, mechanisms, and therapeutic implications of METTL14 in human cancer

“…The proliferation of CD8 + T cells and the production of interferon (IFN)-C, CXCL9, and CXCL10 were also induced. It also promotes the accumulation of CD8 + and CD4 + effector T cells, which inhibit tumor growth, and enhance the efficacy of immunotherapy [ 150 , 151 ]. In the treatment of AML, all-trans retinoic acid/arsenic trioxide (ATO) [ 152 ], differentiation inducers (OP9 medium) [ 153 ], PMA [ 154 ], and all-trans retinoic acid (ATRA) [ 155 ] have been reported to significantly reduce m 6 A levels and the expression of METTL14, thereby promoting myeloid differentiation and inhibiting leukemia growth [ 156 ].…”