METTL1 (Methyltransferase 1, TRNA Methylguanosine)

Mechanistically, Astragalin upregulated miR-193a-5p, and its mimic suppressed METTL1 and COX-2 expression in SiHa cells, whereas its inhibitor restored. Collectively, these findings demonstrate that Astragalin induces apoptosis through miR-193a-5p-mediated inhibition of the METTL1/COX-2 signaling axis, highlighting its potential as a promising antitumor candidate for cervical cancer.

The oesophagus cancer line OE33 shows no proliferative defect upon METTL1/WDR4 loss, despite complete lack of m 7 G46 on its tRNA. OE33 coordinates codon usage and abundance of cognate tRNAs in the absence of METTL1/WDR4; the METTL1/WDR4 sensitive line, OE21, fails to do so.Depleting dihydrouridine synthases (DUS-L) renders OE33 sensitive to METTL1/WDR4 loss.OE33 responds to lack of METTL1/WDR4 activity by upregulating DUS3L and its activity (D47) on tRNA; the sensitive line OE21 fails to do so.METTL1-sensitive lines have intrinsically low DUS3L and cannot sustain higher levels.DUS3L reveals as a potential biomarker for METTL1 sensitivity.

m7G-driven selective regulation exerts context-dependent, two-sided effects on tumour progression. m7G modulates therapeutic response, shaping chemosensitivity and resistance. m7G holds substantial clinical promise as a diagnostic/prognostic biomarker and a therapeutic target.

Our findings reveal an important role of METTL1-mediated internal mRNA m7G modification in promoting synovial aggression of RA, suggesting that METTL1 might be a potential target for therapy of RA, even other dysregulated FLS-associated diseases.

This study reveals that METTL1 and WDR4 are overexpressed in PCa and that, in DU145 cells, their knockdown was associated with suppressed m7G modification and attenuated oncogenic phenotypes. These model-specific findings suggest that METTL1/WDR4 may represent potential therapeutic targets in prostate cancer.

To target these epigenetic vulnerabilities, innovative carrier-free nano-epidrugs (siMBD-R NPs) are developed, incorporating first-line doxorubicin (DOX) with siRNA against METTL1 (siMETTL1), FDA-approved HDAC inhibitor belinostat (BEL), and DSPE-PEG2000-cRGD. In vivo studies demonstrate that siMBD-R NPs can significantly potentiate chemosensitivity, achieving an 81.5% relative increase in tumor inhibition, and can activate an immune response. This work highlights the potential benefits of leveraging dual-targeted epigenetic intervention to evoke osteosarcoma chemosensitization.

In conclusion, POU4F1 drives anti-PD-1 resistance in melanoma by enhancing glycolysis via METTL1-mediated m7G methylation of PKM2. Targeting the POU4F1-METTL1-PKM2 axis may improve melanoma immunotherapy outcomes.

This work provides evidence that multitargeted METTL may have stronger inhibition of HCC cell proliferation. Further in vivo validation, toxicity analysis as well as molecular insights will determine the therapeutic utility against HCC.

Furthermore, integrating epitranscriptomic profiles into genomic risk frameworks may also improve disease stratification, minimal residual disease (MRD) monitoring, and the identification of targetable vulnerabilities. Together, these insights position RNA modifications as central to blood cancer biology and support their integration into next-generation diagnostic, prognostic, and therapeutic strategies.

© 2025 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland

Furthermore, METTL1/WDR4-mediated m7G modification of SCLT1 regulates gefitinib resistance by activating the NF-κB signaling. Our findings reveal the crucial role of aberrant mRNA internal m7G modification in EGFR-TKIs resistance, suggesting that targeting the METTL1/WDR4-SCLT1-NF-κB axis holds a promising therapeutic potential for overcoming EGFR-TKIs resistance.

PGK1 overexpression counteracted the inhibition of glioma cell proliferation and glycolysis induced by METTL1 knockdown. In conclusion, METTL1 functions as an oncogene to accelerate glioma progression by promoting m7G modification of PGK1, providing a potential therapeutic target for glioma.