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Review
. 2023 Jun 23;15(13):3307.
doi: 10.3390/cancers15133307.

The Regulation of m6A Modification in Glioblastoma: Functional Mechanisms and Therapeutic Approaches

Simon Deacon  1   2 , Lauryn Walker  1 , Masar Radhi  1 , Stuart Smith  1   2
Affiliations
Review

The Regulation of m6A Modification in Glioblastoma: Functional Mechanisms and Therapeutic Approaches

Simon Deacon et al. Cancers (Basel). .

Abstract

Glioblastoma is the most prevalent primary brain tumour and invariably confers a poor prognosis. The immense intra-tumoral heterogeneity of glioblastoma and its ability to rapidly develop treatment resistance are key barriers to successful therapy. As such, there is an urgent need for the greater understanding of the tumour biology in order to guide the development of novel therapeutics in this field. N6-methyladenosine (m6A) is the most abundant of the RNA modifications in eukaryotes. Studies have demonstrated that the regulation of this RNA modification is altered in glioblastoma and may serve to regulate diverse mechanisms including glioma stem-cell self-renewal, tumorigenesis, invasion and treatment evasion. However, the precise mechanisms by which m6A modifications exert their functional effects are poorly understood. This review summarises the evidence for the disordered regulation of m6A in glioblastoma and discusses the downstream functional effects of m6A modification on RNA fate. The wide-ranging biological consequences of m6A modification raises the hope that novel cancer therapies can be targeted against this mechanism.

Keywords: RNA methylation; epitranscriptomics; glioblastoma.

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Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
The METTL3–METTL14 heterodimer and associated proteins form the m6A writer complex, whereas FTO and ALKBH5 erase the modification. The m6A modification has a variable effect on mRNA fate, mediated via specific reader proteins.
Figure 2
Figure 2
R-loops are a tripartite structure consisting of a DNA:RNA hybrid and a strand of displaced DNA. The RNA can be m6A methylated, modifying R-loop fate. This process may have a role in genomic instability in the pathogenesis of glioblastoma.
See this image and copyright information in PMC

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References

    1. Boulias K., Greer E.L. Biological roles of adenine methylation in RNA. Nat. Rev. Genet. 2022;24:143–160. doi: 10.1038/s41576-022-00534-0. - DOI - PMC - PubMed
    1. Dominissini D., Moshitch-Moshkovitz S., Schwartz S., Salmon-Divon M., Ungar L., Osenberg S., Cesarkas K., Jacob-Hirsch J., Amariglio N., Kupiec M., et al. Topology of the human and mouse m6A RNA methylomes revealed by m6A-seq. Nature. 2012;485:201–206. doi: 10.1038/nature11112. - DOI - PubMed
    1. Meyer K.D., Saletore Y., Zumbo P., Elemento O., Mason C.E., Jaffrey S.R. Comprehensive Analysis of mRNA Methylation Reveals Enrichment in 3′ UTRs and near Stop Codons. Cell. 2012;149:1635–1646. doi: 10.1016/j.cell.2012.05.003. - DOI - PMC - PubMed
    1. Tegowski M., Flamand M.N., Meyer K.D. scDART-seq reveals distinct m6A signatures and mRNA methylation heterogeneity in single cells. Mol. Cell. 2022;82:868–878.e10. doi: 10.1016/j.molcel.2021.12.038. - DOI - PMC - PubMed
    1. Shi H., Wei J., He C. Where, When, and How: Context-Dependent Functions of RNA Methylation Writers, Readers, and Erasers. Mol. Cell. 2019;74:640–650. doi: 10.1016/j.molcel.2019.04.025. - DOI - PMC - PubMed