YTHDF3 suppresses interferon-stimulated gene (ISG)-dependent antitumor immunity and promotes HPV carcinogenesis in cervical cancer.

ABSTRACT: Interferon-stimulated genes (ISGs) serve as evolutionarily conserved mediators of antiviral defense and tumor surveillance. Emerging evidence underscores the non-oncogenic addiction of high-risk human papillomavirus (hrHPV) E6/E7 oncoproteins in maintaining malignant phenotypes and cervical carcinogenesis. Here, we leveraged CRISPR/Cas9-engineered YTHDF3-knockout (YTHDF3^-/-) SiHa cells and Ythdf3^-/- mice to dissect the molecular arbiters governing m⁶A-dependent RNA regulation in HPV-driven carcinogenesis. To further elucidate the role of YTHDF3 in HPV-induced immunosuppressive tumor microenvironment (ITME) formation, we demonstrated that YTHDF3, an m⁶A RNA reader, suppresses type I ISGs responses. Notably, elevated m⁶A modification and

SUBMITTER: Li L 

PROVIDER: S-EPMC12827990 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature