{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T17:42:59Z","timestamp":1793209379691,"version":"4.5.0"},"reference-count":49,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T00:00:00Z","timestamp":1741651200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Hefei municipal Natural Science Foundation","award":["2022050"],"award-info":[{"award-number":["2022050"]}]},{"name":"Hefei municipal Natural Science Foundation","award":["2023032"],"award-info":[{"award-number":["2023032"]}]},{"name":"Hefei municipal Natural Science Foundation","award":["WJ2023CYHXM04"],"award-info":[{"award-number":["WJ2023CYHXM04"]}]},{"name":"Wanjiang Emerging Industry Technology Development Center","award":["2022050"],"award-info":[{"award-number":["2022050"]}]},{"name":"Wanjiang Emerging Industry Technology Development Center","award":["2023032"],"award-info":[{"award-number":["2023032"]}]},{"name":"Wanjiang Emerging Industry Technology Development Center","award":["WJ2023CYHXM04"],"award-info":[{"award-number":["WJ2023CYHXM04"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>NF-\u03baB, a multifunctional transcription factor, is linked to cancer initiation and progression. As a key immune mediator, it may play a crucial role in HPV-induced cervical carcinogenesis. However, consensus is lacking on the activation timing of NF-\u03baB during the transition from cervical intraepithelial neoplasia (CIN) to cervical squamous cell carcinoma (CSCC). In this study, immunohistochemical analysis was performed to examine RELA, one of the important members of the NF-\u03baB family, and phospho-RELA expression in different cervical lesions. Then, we analyzed NF-\u03baB regulation of differentially expressed genes (DEGs) in cervical lesions vs. normal tissues. Gene enrichment identified oncogenic DEGs, followed by expression and survival analyses. The impact of NF-\u03baB activation on cervical cell proliferation, migration, and oncogenic regulation, as well as the effects of inhibiting NF-\u03baB, were examined. Our study showed that NF-\u03baB activation starts in cervical simple hyperplasia and intensifies as CIN evolves to CSCC. NF-\u03baB-regulated DEGs show stage-specific functions: immune regulation in CIN and cancer promotion in CSCC. Short-term NF-\u03baB activation boosts cervical cell proliferation and migration, which is reversible by an NF-\u03baB inhibitor. Long-term NF-\u03baB activation promotes the expression of cancer-promoting genes in normal cells and also maintains them in cancer tissues, which is linked to poorer prognosis. Inhibiting NF-\u03baB downregulates these genes in cancer cells and suppresses the oncogenic abilities of cervical cancer cells. Collectively, NF-\u03baB activation initiates during the simple hyperplasia stage of cervical cells, stimulating proliferation, migration, and oncogene expression. Throughout the transition from CIN to CSCC, NF-\u03baB activation progressively intensifies, and its long-term activation promotes carcinogenesis. Thus, NF-\u03baB is crucial in mediating cervical oncogenic transformation.<\/jats:p>","DOI":"10.3390\/ijms26062493","type":"journal-article","created":{"date-parts":[[2025,3,11]],"date-time":"2025-03-11T06:52:30Z","timestamp":1741675950000},"page":"2493","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["NF-\u03baB Activation Is Essential for Cervical Cell Proliferation and Malignant Transformation"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-0048-4788","authenticated-orcid":false,"given":"Hui","family":"Chen","sequence":"first","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Science Island Branch, Graduate School of University of Science and Technology of China, Hefei 230026, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qianwen","family":"Cui","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Science Island Branch, Graduate School of University of Science and Technology of China, Hefei 230026, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6520-7182","authenticated-orcid":false,"given":"Wulin","family":"Yang","sequence":"additional","affiliation":[{"name":"Anhui Province Key Laboratory of Medical Physics and Technology, Institute of Health and Medical Technology, Hefei Institutes of Physical Science, Chinese Academy of Sciences, Hefei 230031, China"},{"name":"Science Island Branch, Graduate School of University of Science and Technology of China, Hefei 230026, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"229","DOI":"10.3322\/caac.21834","article-title":"Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries","volume":"74","author":"Bray","year":"2024","journal-title":"CA Cancer J. 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