m6A modification in RNA: biogenesis, functions and roles in gliomas

Abstract

The chemical modification of RNA is a newly discovered epigenetic regulation mechanism in cells and plays a crucial role in a variety of biological processes. N6-methyladenine (m6A) mRNA modification is the most abundant form of posttranscriptional RNA modification in eukaryotes. Through the development of m6A RNA sequencing, the relevant molecular mechanism of m6A modification has gradually been revealed. It has been found that the effect of m6A modification on RNA metabolism involves processing, nuclear export, translation and even decay. As the most common malignant tumour of the central nervous system, gliomas (especially glioblastoma) have a very poor prognosis, and treatment efficacy is not ideal even with the application of high-intensity treatment measures of surgery combined with chemoradiotherapy. Exploring the origin and development mechanisms of tumour cells from the perspective of tumour biogenesis has always been a hotspot in the field of glioma research. Emerging evidence suggests that m6A modification can play a key role in gliomas through a variety of mechanisms, providing more possibilities for early diagnosis and targeted therapy of gliomas. The aim of the present review is to focus on the research progress regarding the association between m6A modification and gliomas. And to provide a theoretical basis according to the currently available literature for further exploring this association. This review may provide new insights for the molecular mechanism, early diagnosis, histologic grading, targeted therapy and prognostic evaluation of gliomas.

Screening and functional prediction of differentially expressed circular RNAs in human glioma of different grades

“…Recently, m 6 A was reported to mediate the biogenesis of coding circRNAs [ 20 ] and could modulate cytoplasmic export and promote CRC liver metastasis [ 60 ]. The functional crosstalk and their function in tumor regulation between non-coding RNAs (miRNA, lncRNA, and circRNA) and m 6 A have been explored [ 16 , 61 ]. Hence, the analysis and validation of m 6 A in circRNAs requires further research.…”

“…N6-methyladenine (m 6 A) modification is the most abundant form of posttranscriptional RNA modification in eukaryotes. In recent years, the role of m 6 A in cancers including gliomas has been gradually recognized [ 16 , 17 ]. It has been reported that N6-methyladenosine (m 6 A) modification could also initiate the translation of circRNAs [ 18 ].…”

Molecular Characteristics, Prognostic Value, and Immune Characteristics of m6A Regulators Identified in Head and Neck Squamous Cell Carcinoma

“…In addition to these traditional epigenetic modifications, mRNA modification is known as another epigenetic regulation of gene expression. Its dynamic regulation and disorder are closely related to translation control, RNA splicing defects, and the occurrence, maintenance, and progression of various tumors ( 3 , 4 ). The degree of RNA modification is highly sensitive to changes in the cell microenvironment or the transformation of physiological states, and RNA modification changes will in turn influence cell regulation and adaptation ( 5 ).…”

The m6A RNA Demethylase ALKBH5 Promotes Radioresistance and Invasion Capability of Glioma Stem Cells

“…Methyltransferases METTL3/METTL14 and their co-factors, also known as m6A “writers”, catalyze the formation of m6A, whereas the demethylases FTO and ALKBH5, named m6A “erasers”, selectively remove m6A modifications. These modifications regulate the splicing, stability, and translation efficiency of specific subsets of mRNA targets [ 6 ]. Abnormal expression of m6A regulators has been reported in different cancers and associated in particular with cell proliferation and maintenance of cancer stem cells [ 7 , 8 , 9 , 10 ].…”