Research progress concerning m⁶A methylation and cancer (Review)

Abstract

N6-methyladenosine (m 6 A) methylation is a type of methylation modification on RNA molecules, which was first discovered in 1974, and has become a hot topic in life science in recent years. m 6 A modification is an epigenetic regulation similar to DNA and histone modification and is dynamically reversible in mammalian cells. This chemical marker of RNA is produced by m 6 A 'writers' (methylase) and can be degraded by m 6 A 'erasers' (demethylase). Methylated reading protein is the 'reader', that can recognize the mRNA containing m 6 A and regulate the expression of downstream genes accordingly. m 6 A methylation is involved in all stages of the RNA life cycle, including RNA processing, nuclear export, translation and regulation of RNA degradation, indicating that m 6 A plays a crucial role in RNA metabolism. Recent studies have shown that m 6 A modification is a complicated regulatory network in different cell lines, tissues and spatio-temporal models, and m 6 A methylation is associated with the occurrence and development of tumors. The present review describes the regulatory mechanism and physiological functions of m 6 A methylation, and its research progress in several types of human tumor, to provide novel approaches for early diagnosis and targeted treatment of cancer.

Decreased Expression of Programmed Death Ligand-L1 by Seven in Absentia Homolog 2 in Cholangiocarcinoma Enhances T-Cell–Mediated Antitumor Activity

“…We also demonstrated the increased m6A modification on the 3'UTR region of the METTL4-induced PD-L1 mRNA in CCA cells. It has been documented that m6A modification affects mRNA stability, splicing, nuclear export, and/or translation of target mRNAs, depending on the distinct proteins that recognize them [e.g., YTHDF1, YTHDF2, YTHDF3 (6)]. We have shown that decreasing Siah2 mRNA levels by METTL14 were mainly due to the accelerated degradation of Siah2 mRNA, depending on the m6A reader protein YTHDF2, thereby decreasing Siah2 protein level.…”

“…Thirteen weeks after CD34+ cell injection, CD34+ humanized NCG mice were randomly assigned into experiment groups. Indicated CCA cells with LV-NC/LV-METTL14 of 5×10 6 were injected into the right flank of CD34+ humanized NCG mice. Tumor volume was calculated by the following formula: volume = ab2/2 (a, the longer axis; b, the shorter axis).…”

“…RNA N6-methyladenosine (m6A) is the most abundant internal modification in mRNAs, which is widely present in mammal cells and mainly present in the last exon of mRNA (5). Its methylation is regulated by "writer," "eraser," and "reader" proteins (6). In addition, m6A methyltransferase complex is mainly composed of METTL3 (methyltransferase-like 3), METTL14 (methyltransferase-like 14), and WTAP (Wilms tumor 1-associated protein), which act as "writer" to catalyze methylation processes, whereas FTO (fat mass and obesity associated protein) and ALKBH5 (alkB homolog 5) act as demethylases ("eraser").…”

Modification of m6A mediates tissue immune microenvironment in calcific aortic valve disease

“…These proteins may broadly be divided into 3 categories: writer complexes, m6A demethylases, and function executions (readers). Within these categories, WTAP, RBM15, RBM15B, METTL3, METTL14, METTL16, and KIAA1429 are among the writer complexes; FTO and ALKBH5, the 2 evaluated m6A demethylases, are among the erasers; HNRNPs, YTHDF1, YTHDF2, YTHDF3, YTHDC1, YTHDC2, YTHDC3, EIF3A, IGF2BP1, IGF2BP2, and IGF2BP3 are among the function executions (readers) (23)(24)(25)(26). Recent studies have shown that m6A is required for a wide range of biological activities, including viral infection (27,28), stress (29), heat shock (30), and DNA damage (31).…”

RBM10, a new potential RBP function, recruits METTL3 to induce N6-methyladenosine-MALAT1-dependent modification on inhibiting the invasion and migration of NSCLC

“…[9] Studies have proved that the abnormal regulation mechanism can induce the abnormal expression of downstream target genes and eventually lead to tumor. [10] M6A methylation is composed of methyltransferases (writers), demethylases (erasers) and m6A binding proteins (readers). [11] Once these enzymes are abnormal, they will cause a series of diseases, including cancer, neurological diseases and embryonic retardation.…”