YTHDF2 (YTH N6-Methyladenosine RNA Binding Protein 2)

Functionally, YTHDF2 promoted malignant phenotypes in keratinocytes and exacerbated arsenic-induced skin lesions in mice, accompanied by activation of the PRR5-mTORC2-AKT axis and enhancement SMAD2/3 signaling. This study advances our understanding of how opposing m6A regulatory axes shape YTHDF2 engagement and mRNA decay outputs, thereby promoting arsenic carcinogenesis by regulating oncogenic and tumor-suppressive signaling.

Furthermore, we identify sodium 2, 2-dichloroacetate (DCA) as a novel inhibitor of USP30, and DCA inhibits CRC serine synthesis and tumor growth. Clinically, USP30, FTO, PHGDH, and PSAT1 levels are highly correlated in CRC tissues. This study provides mechanistic insights into how USP30 senses serine/glycine levels to regulate serine synthesis via the FTO-PHGDH/PSAT1 axis, offering a potential therapeutic strategy for targeting serine/glycine metabolism in cancer.

METTL3 enhances AFAP1-AS1 stability via m6A modification recognized by YTHDF2 and IGF2BP1, which subsequently increases EGR2 expression by improving its mRNA stability. EGR2 directly activates transcription of immune checkpoint and epithelial-mesenchymal transition (EMT)-related genes. This METTL3/AFAP1-AS1/EGR2 signaling axis drives PC malignancy and immune resistance, offering potential therapeutic targets for PC treatment.

Our systematic machine learning analysis demonstrates that m6A regulators can effectively predict CRC prognosis and immunotherapy response. The eight-gene signature provides a practical tool for clinical risk assessment and treatment decision-making.

These findings suggest that m6A-mediated regulation of CCL20 in S. aureus-induced BMECs operates via the PI3K/Akt/NF-κB pathway. These findings underscore the significance of m6A-mediated CCL20 regulation in mastitis pathogenesis and suggest potential therapeutic strategies for managing this economically significant disease in dairy farming.

Collectively, these findings support a model in which an irradiation-responsive YTHDF2-DHRS3-LRAT axis assembles a retinoid-coupled NADPH module at endoplasmic reticulum (ER)-lipid-droplet (LD)-mitochondria interfaces to limit oxidative stress and contribute to radioresistance. Mechanistic experiments illustrate how this pathway buffers irradiation-induced oxidative stress across transcriptomic, biochemical, and imaging readouts, suggesting that targeting YTHDF2 or the DHRS3-LRAT node may offer a tractable strategy to improve radiotherapy in esophageal squamous cell carcinoma.

In vivo, the anti-leukemic efficacy of HHT was significantly diminished upon EWSR1 knockdown, demonstrating that EWSR1 was required for therapeutic response. Collectively, these findings uncover a phase separation-centric mechanism by which HHT exerts anti-AML activity, establish the EWSR1-YTHDF2-m6A axis as a critical regulator of leukemia progression, and position EWSR1 as both a functional target and a predictive biomarker for optimizing HHT-based therapies.

Mechanistically, YTHDF2 enhanced the PCa progression and metastasis by modulating the m6A methylation of CDKN1C mRNA. Together, these findings suggest that Fbxo2 axis may serve as a potential prognostic marker and therapeutic target in PCa.

Notably, TNF-α downregulated HDAC5 by promoting WTAP-mediated m6A modification of HDAC5 mRNAs, which are subsequently regulated by YTHDF2 to reduce mRNA stability. Our results reveal a synergistic epigenetic regulatory mechanism between SEs and m6A modification of MSC immunosuppressive functions and provide a novel strategy to promote the clinical therapeutic potential of MSC infusion in inflammatory diseases.

Our findings reveal a novel regulatory YTHDF2-SREBF1 axis that links m6A-dependent post-transcriptional regulation to ferroptosis modulation through lipid metabolic remodeling. Therapeutically targeting the YTHDF2-SREBF1 pathway may represent a promising strategy to overcome radiotherapy resistance in ATC through metabolic intervention.

However, its effect on viral replication is complex and context-dependent, exhibiting both proviral and antiviral functions under different cellular environments. This review highlights current insights into how YTHDF2 modulates the replication of various viruses and discusses its broader implications in host-virus interactions.

These findings show that DjYTHDF2.2 promotes neoblast self-renewal and regeneration by targeting Djast mRNA for degradation, which is a novel m6A-dependent regulatory axis that is essential for stem cell maintenance and tissue regeneration in planarians. This study highlights the conserved role of YTHDF2-mediated post-transcriptional control in stem cell biology and regenerative mechanisms.