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Through immunohistochemical staining and immunoblotting, CCK\u20108 viability assays, EdU incorporation tests, clonogenic survival experiments, flow cytometric detection, transmission electron microscopy, immunofluorescence staining and heterotopic transplantation model, we discover that IRF4 expression was markedly decreased in cervical cancer tissues and cell lines compared to normal controls. Overexpression of IRF4 suppressed proliferation, migration, and invasion in both Siha and HeLa cells, while concurrently enhancing radiosensitivity. Mechanistically, IRF4 upregulated autophagy\u2010related proteins (LC3, Beclin\u20101) and promoted autophagosome formation, while downregulating P62 by inhibiting the PI3K\/Akt\/mTOR pathway. In\u00a0vivo studies demonstrated that IRF4 augmented the tumor response to radiation and further potentiated the effects when combined with rapamycin treatment, confirming its pivotal role in promoting radiosensitivity through PI3K\/Akt\/mTOR\u2010mediated autophagy. IRF4 emerges as a critical regulator of cervical cancer progression via modulation of autophagy and influences the tumor's response to radiotherapy. It holds promise as a potential therapeutic target to enhance cervical cancer radiosensitivity.<\/jats:p>","DOI":"10.1111\/cas.70305","type":"journal-article","created":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T04:16:17Z","timestamp":1768882577000},"page":"958-971","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["IRF4 Enhances Radiosensitivity of Cervical Cancer by Inhibiting the PI3K\/Akt\/mTOR Pathway to Regulate Autophagy"],"prefix":"10.1111","volume":"117","author":[{"given":"Meihui","family":"Gao","sequence":"first","affiliation":[{"name":"Department of Gynecology Clinical Oncology School of Fujian Medical University, Fujian Cancer Hospital  Fuzhou Fujian China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaolei","family":"Cui","sequence":"additional","affiliation":[{"name":"Laboratory of Biochemistry and Molecular Biology Research, Department of Laboratory Medicine Clinical 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