Table 1 Dysfunction associated with RNA modifications in glioma
RNA modification | Regulator | Target genes/pathways | Effect on glioma development | Sources |
|---|---|---|---|---|
m6A | YTHDC1 | Prevents NMD of arginine rich SRSF3 transcripts | Promotes proliferation and progression in primary cells | [109] |
YTHDF2 | Stabilized by EGFR/SRC/ERK pathway Facilitates mRNA decay of LXRα and HIVEP2 Stabilizes MYC and VEGFA transcripts | Promotes proliferation, invasion, and tumorigenesis in GSCs | ||
HNRNPA2B1 | Activates AKT and STAT3 signaling pathway Enhances expression of Bcl-2 and PCNA | Promotes proliferation and inhibits apoptosis in cell line and xenograft mouse | [112] | |
METTL3 | Modulates Bcl-2 and SRSF protein expression to regulate apoptosis | Promotes proliferation and progression in cell line, primary cells, and xenograft mice | ||
ALKBH5 | Stabilizes G6PD Activates pentose phosphate pathway Enhances SOX2 and FOXM1 expression | Promotes proliferation in cell lines | ||
FTO | Inhibited by 2-HG secondary to IDH1 mutations Stabilizes c-Myc and CEBPA Decreases VPS25 expression | Context dependent. Tumorigenic role both when inhibited (hyper-m6A-methylation) and not with growth factor stabilization. Reduces glioma growth by increased glioma apoptosis | ||
m1A | TRMT6 | Regulates cell cycle, PI3K-AKT, TGF-beta, MTORC1, NOTCH, and MYC pathway | Promotes proliferation, migration, and invasion in rat and human cell lines | |
TRMT61A | Targeted by HIF1A target Suppressed by c-Myc inhibition (hypoxic conditions) | Promotes proliferation in rat cell line | ||
m5C | NOP2 NSUN4/5/7 | – | Worsens prognosis | [123] |
NSUN6 | – | Improves prognosis | [123] | |
A-to-I RNA Editing | ADAR1/ADAR | Prevents aberrant RLR activation Prevents PKR activation Edits GM2A | Promotes GSC proliferation and self-renewal in primary cells and xenograft mice Negatively associated with grade | |
ADAR2/ADARB1 | Edits GRIA2 Edits CDC14B pre-mRNA Reduces Skp2/p21/p27 cell cycle pathway | Inhibits proliferation and migration in cell lines Negatively associated with grade | ||
ADAR3/ADARB2 | Inhibits (competitively) ADAR1/2 Promotes NF-κB activation | Promotes proliferation and progression in cell lines | ||
ψ | PUS7 | Modulates TYK2–STAT1 pathway | Promotes proliferation and progression in GSCs and xenograft mice | |
DKC1 | Upregulates HIF1A, N-cadherin, and MMP-2 | Inhibits proliferation, migration, and invasion in cell lines | [130] |