ArticleJournal of gastrointestinal oncology2025
YTHDF1 regulates YTHDF2 stability via m6A-dependent mechanisms in hepatocellular carcinoma: insights from
Article in Journal of gastrointestinal oncology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Ubiquitination and NOncology letters · 2026Review
- mArXiv · 2026Article
- The m6A Reader YTHDF3 Promotes Glioma Progression by Regulating the m6A Modification of lncRNA-PAR5.Analytical cellular pathology (Amsterdam) · 2026Article
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Hepatocellular carcinoma (HCC) maintains a significant mortality burden, primarily attributable to the lack of validated prognostic molecular signatures. While N6-methyladenosine (m6A) reader proteins, especially YT521-B homology domain family proteins (YTHDFs), show emerging relevance in oncogenesis, their regulatory interplay and clinical utility as combinatorial biomarkers remain unclear. Our study aimed to explore the regulatory network and clinical relevance of YTHDF paralogs in HCC. Methods: Spatial co-expression patterns were analyzed via immunohistochemistry and spatial transcriptomics in HCC tissues. Protein/RNA levels of YTHDFs were quantified by western blot and quantitative real-time polymerase chain reaction (PCR). RNA immunoprecipitation (RIP), enhanced crosslinking and immunoprecipitation (e-CLIP) sequencing, dual fluorescence reporter assay, and RNA stability experiments were conducted to verify underlying regulatory mechanisms. Univariate and multivariate Cox regression analysis and Kaplan-Meier survival analysis were utilized to estimate the potential clinical significances. Results: YTHDF1 overexpression correlated with poor prognosis and emerged as the strongest prognostic marker among the YTHDF paralogs. YTHDF1 could bind to the messenger RNA (mRNA) of YTHDF2 and YTHDF3 at specific m6A sites. However, Conclusions: YTHDF1 drives HCC progression through m6A-mediated stabilization of YTHDF2, revealing their functional synergy. Their combined spatial and expression profiles offer a superior prognostic biomarker, suggesting novel therapeutic targets.
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