Functions of N6-methyladenosine and its role in cancer

Abstract

N6-methyladenosine (m6A) is methylation that occurs in the N6-position of adenosine, which is the most prevalent internal modification on eukaryotic mRNA. Accumulating evidence suggests that m6A modulates gene expression, thereby regulating cellular processes ranging from cell self-renewal, differentiation, invasion and apoptosis. M6A is installed by m6A methyltransferases, removed by m6A demethylases and recognized by reader proteins, which regulate of RNA metabolism including translation, splicing, export, degradation and microRNA processing. Alteration of m6A levels participates in cancer pathogenesis and development via regulating expression of tumor-related genes like BRD4, MYC, SOCS2 and EGFR. In this review, we elaborate on recent advances in research of m6A enzymes. We also highlight the underlying mechanism of m6A in cancer pathogenesis and progression. Finally, we review corresponding potential targets in cancer therapy.

m6A-dependent glycolysis enhances colorectal cancer progression

“…Recent studies have shown that m 6 A modification in mRNAs participates in RNA metabolisms to regulate mRNA stability, splicing, transport, localization, as well as in stem cell self-renewal and differentiation, tissue development in normal cellular physiological and disease status [10,[17][18][19]. Recent studies have reported that the writers, readers, and erasers of m 6 A may play important roles in various cancer initiation, progression and response to immunotherapy via different regulation patterns [18,[20][21][22][23][24]. Despite these recent discoveries between m 6 A modification with malignant cancer development and treatment, the status of m 6 A modification and the underlying regulatory mechanism in CRC, especially in the glycolytic metabolism of CRC remains little known.…”

YTHDF2, a protein repressed by miR-145, regulates proliferation, apoptosis, and migration in ovarian cancer cells

“…Increasing evidence shows that the methylation of m6A mRNA is closely related to the occurrence and development of tumors. The expression level of m6Arelated protein is an important regulatory factor that directly determines the pathological process of tumor development [6]. However, the m6A modi cation in the regulation of EOC is still poorly understood.…”

“…RNA methylation can reverse the methylation modi cation at the RNA level, which is an extremely important epigenetic modi cation [4]. Further, 6-methyladenine (m6A) is the most abundant methylation modi cation of mRNA in eukaryotic cells, involving the participation of three types of molecules: methyltransferase complex (METTL3, METTL14, and WTAP), named as "Writers"; demethylase (FTO and ALKBH5), named as "Erasers"; and m6A-modi ed binding protein (YTHDF1/2/3), named as "readers", which can dynamically and reversibly regulate the m6A level [5,6]. In 2017, Professor Chuan's research team found that m6A was involved in the regulation of self-renewal and differentiation of glioblastoma stem cells (GSCs).…”

Construction of a m6A RNA Methylation Regulator-related Signature for Prognosis and Immune Response in Lung Adenocarcinoma

“…In addition, another study also demonstrates the overexpression of METTL3 can dramatically suppress proliferation, migration and invasion for colorectal carcinoma (CRC) cells [25]. Thus, m6A regulator genes are not only promising to become the potential molecular markers for cancer diagnosis and prognosis, but also quali ed to serve as the targets for the design of targeted anticancer drugs, which has been demonstrated in several literatures [26][27][28]. Several studies have investigated the role of m6A regulator genes in the survival of cancers, such as glioma [29], gastric cancer [30], and head and neck squamous cell carcinoma [31].…”