H3K27me3 loss and METTL3-m6A converge to upregulate SOX11/SMARCA4 and drive H3K27-altered spinal cord glioma stemness and proliferation

Clicks: 20
ID: 330000
2026
Free PDF
Article Quality & Performance Metrics
Overall Quality
Not rated
Combines reader engagement with the AI quality analysis. This article has not been analysed, so there is no overall score — reader engagement is measured and shown alongside.
AI Quality Assessment
Not analyzed
Readership in this journal
Emerging

Ranked #167 of 286 articles by views in journal of neuro-oncology

Most read Least read

Bar heights use a square-root scale. Only the 120 most-read articles are drawn; the journal has 286 in total.

Mint this article as an NFT
Not yet minted

Create a permanent, verifiable on-chain record of this article on the Scimatic Network. The NFT is held in your Journament account, and you can withdraw it to your own wallet at any time.

5 SUSD one-off · no wallet required
Sign in to mint
Abstract
Abstract Background H3 K27-altered diffuse midline gliomas (H3-DMGs) are driven by stem-like and proliferative tumor cells resulting from global H3K27me3 loss. Here, we aimed to identify key molecular mechanisms involved in the interplay between epigenetic and epitranscriptomic regulation underlying this process. Methods Patient-derived spinal cord H3-DMG stem-like spheres and serum-induced differentiated cells were used to model tumor plasticity. Multi-omics approaches, including single-cell RNA sequencing, spatial transcriptomics, RNA m6A profiling, CUT&Tag, ATAC-seq, and in vitro and in vivo assays were performed to dissect epigenetic and epitranscriptomic regulation of stemness. Results Differentiation reduced stemness markers, proliferation, H3K27M expression, and global m6A levels, while increasing H3K27me3. METTL3 was significantly downregulated during differentiation and positively correlated with stemness and proliferation in patient tumors. METTL3 promoted tumor stemness and growth by stabilizing SOX11 mRNA through YTHDC2-dependent m6A recognition. In parallel, H3K27me3 loss relieved transcriptional repression at both METTL3 and SOX11 loci, leading to SOX11 overexpression. Functionally, SOX11 interacted with SMARCA4, the core ATPase of the SWI/SNF complex, to enhance chromatin accessibility and activate stemness-associated transcriptional programs marked by H3K27ac and H3K4me3 enrichment. Clinically, METTL3 and SOX11 were upregulated in H3K27M-mutant tumors, and high SOX11 expression correlated with increased proliferation, poor prognosis, and enhanced sensitivity to the SMARCA4 inhibitor BRM014. Conclusions H3K27M-driven epigenetic dysregulation promotes SOX11 overexpression through combined H3K27me3 loss and METTL3-mediated m6A modification. SOX11 sustains tumor stemness and proliferation by recruiting SMARCA4 to remodel chromatin and serves as both a prognostic biomarker and a predictor of response to SMARCA4-targeted therapy in spinal cord H3-DMG.
Reference Key
openalex_W7214674205 Use this key to autocite in the manuscript while using SciMatic Manuscript Manager or Thesis Manager
Authors Hao Yan, Jialin Jin, Yuzhou Chang, Bo Pang, Han Lin, Songyuan An, Lanhui Zheng, Boping Liu, Yilin Wu, Wenhao Xia, Bing Sun, Yantao Liu, Xiaoyang Qin, 贾文清, Ruichao Chai, Yongzhi Wang
Are you one of these authors? Claim your profile
Journal journal of neuro-oncology
Year 2026
DOI
10.1093/neuonc/noag232
URL
https://doi.org/10.1093/neuonc/noag232
Keywords Keywords not found

Citations

No citations found. To add a citation, contact the admin at info@scimatic.org

Comments

No comments yet. Be the first to comment on this article.