Abstract
Emerging evidence shows that N7-methylguanosine (m(7)G) modification and its writers contribute to the development of diverse cancers. However, the role of m(7)G writers in kidney renal clear cell carcinoma (KIRC) remains unclear. In this study we show that the catalytic components of m(7)G writers, METTL1 and BUD23, are overexpressed in advanced KIRC and are associated with worse overall survival. Knockdown of METTL1 or BUD23 inhibited cell proliferation, colony formation, and migration in KIRC cell lines, indicating their oncogenic role in KIRC. Furthermore, we observed that METTL1 and BUD23 expression was negatively correlated with the expression of key tumor suppressor genes commonly dysregulated in KIRC. We observed METTL1-mediated m(7)G methylation in mRNAs expressed by these tumor suppressor genes, indicating that METTL1 may regulate these genes via m(7)G modification. Overall, our study highlights the oncogenic role of METTL1 and BUD23 in KIRC and their potential as prognostic biomarkers and therapeutic targets in KIRC. © 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.