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Table 1 Role of m6A in glioma pathogenesis

From: The role m6A RNA methylation is CNS development and glioma pathogenesis

Protein Functional classification Known role in brain tumor Molecular mechanism Refs.
METTL3 m6A writer ·The KD of METTL3 or METTL14 enhances GSC's growth, self-renewal and promotes tumor progression. Overexpressing METTL3 Inhibits GSC's growth and self-renewal
·Sustaining oncogenic role
·A potential molecular target
·Indicating RNA processing and coordinating execution of the carcinogenic pathway
·The KD of METTL3 and METTL14, the m6A methyltransferases, induced upregulation of the proto-oncogenes (e.g., ADAM19, EPHA3, and KLF4) and downregulation of the tumor suppressor genes (e.g., CDKN2A, BRCA2 and TP53I11),the astrocyte marker GFAP and neuronal marker TUBB3 were also downregulated, promoting self-renewal, and tumorigenesis of GSCs. METTL3 or METTL14 KD regulated the expression of genes involved in cell proliferation, differentiation, and DNA damage response
·Regulating NMD, the splicing factor, and the alternative splicing switch to maintained carcinogenic effect in GBM
·Enhancing the m6A methylation of SOX2-3'UTR to improve the stability of SOX2,which promotes the stemness maintenance and radiation resistance of GSCs
·The silencing of METTL3 might lead to an abnormal increase in alternative splicing events
METTL14 m6A writer Same as METTL3 Same as METTL3  
WTAP m6A writer ·A regulatory subunit of m6A
·WTAP expression predicts poor prognosis in malignant glioma patients
·Regulating migration and invasion of glioblatoma cells
·Coordinating the localization of METTL3-METTL14 heterodimer to the nuclear speckles, thereby promoting m6A methylation
·Enhancing the proliferation, migration, invasion and tumorigenicity of GSCs in heterografts by mediating the phosphorylation of epidermal growth factor receptor (EGFR) and AKT
·Regulating the expressions of some genes related to cancer cell movements, such as chemotactic ligand 2 (CCL2), chemotactic ligand 3 (CCL3), matrix metallopeptidase 3 (MMP3), lysyl oxidase-like protein 1 (LOXL1), hyaluronan synthase 1 (HAS1), and thrombospondin-1 (THBS1)
ALKBH5 m6A eraser ·ALKBH5 is widely expressed in neurons, decreased during brain development and highly expressed in GSCs ·Inhibiting ALKBH5 would decrease the self-renewal and proliferation of GSCs and tumorigenesis
·ALKBH5 demethylates FOXM1 nascent transcripts. ALKBH5 binds to 3'UTR to upregulate FOXM1 expression. FOXM1-AS, as a nuclear lncRNA (antisense nuclear lncRNA), can further promote the interaction between the FOXM1 nascent transcripts and ALKBH5, thereby accelerating this process. FOXM1-AS knockout also disrupts FOXM1 expression and self-renewal of GSC. After depleting ALKBH5 or FOXM1-AS, inducing FOXM1 expression is a salvage against the growth of GSCs
FTO m6A eraser ·FTO plays a critical oncogenic role in self-renewal of GSCs and is required for the development of GBM ·R-2HG can inhibit the proliferation/survival of FTO-high tumor cells by targeting the FTO/m6A/MYC/ CEBPA pathway [54]