ArticleJournal of experimental & clinical cancer research : CR2025
The BRAF V600E/MEK/ERK/METTL3 positive feedback loop regulates autophagy and promotes stemness and invasiveness in glioblastoma via m
Article in Journal of experimental & clinical cancer research : CR, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
2 citing papers in PubMed.
- The relevance of mJournal of cancer research and clinical oncology · 2026Review
- RNA modifications in cancer stem cells: molecular mechanisms and targeted therapeutic strategies.Frontiers in cell and developmental biology · 2026Review
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Authors and funding
18 authors.
Funding
Abstract
backgroundEpithelioid glioblastoma (GBM) is characterized by its highly aggressive behavior and the presence of the BRAF V600E mutation. However, the impact and underlying mechanisms of the BRAF V600E mutation on GBM stemness and invasiveness are unknown. Dysregulation of N6-methyladenosine (m6A) modification is closely associated with the progression of various cancers. The role of m6A modification in BRAF V600E-mutant GBM has not been defined.
methodsFunctional assays were performed to evaluate the impact of BRAF V600E on stemness phenotypes of glioma stem-like cells (GSCs) and invasive phenotypes of GBM cells in vitro and in vivo. Mechanistic investigations involved m6A quantification, qPCR, western blotting, co-immunoprecipitation, MeRIP-seq, luciferase reporter assays, and transmission electron microscopy to elucidate the mechanism by which BRAF V600E regulates stemness and invasiveness. These findings were further supported by evidence from public GBM patient databases and tumor samples.
resultsWe found that BRAF V600E significantly upregulated METTL3 expression via ERK signaling in GSCs and GBM cells, thereby promoting stemness and invasiveness. METTL3 established a positive feedback loop with BRAF V600E to facilitate m6A modification enrichment, thereby inducing autophagy. The BRAF V600E-driving stemness and invasiveness were autophagy-dependent. In vivo experiments showed that BRAF V600E-expressing GBM was responsive to both the METTL3 inhibitor STM2457 and the autophagy inhibitor HCQ.
conclusionsThis study reveals that the BRAF V600E/MEK/ERK/METTL3 positive feedback loop promotes autophagy, driving the stemness of GSCs and the invasiveness of GBM cells via m6A modification in vitro and in vivo. Our results suggest that METTL3 and autophagy are promising therapeutic targets in BRAF V600E-mutant GBM.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.