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Here, we report that FOXP4 is a new target molecule for differentiation therapy of cervical intraepithelial neoplasia (CIN). An immunohistochemical study showed that FOXP4 was expressed in columnar epithelial, reserve, and immature squamous cells, but not in mature squamous cells of the normal uterine cervix. In contrast with normal mature squamous cells, FOXP4 was expressed in atypical squamous cells in CIN and squamous cell carcinoma lesions. The FOXP4\u2010positive areas significantly increased according to the CIN stages from CIN1 to CIN3. In monolayer cultures, downregulation of FOXP4 attenuated proliferation and induced squamous differentiation in CIN1\u2010derived HPV 16\u2010positive W12 cells via an ELF3\u2010dependent pathway. In organotypic raft cultures, FOXP4\u2010downregulated W12 cells showed mature squamous phenotypes of CIN lesions. In human keratinocyte\u2010derived HaCaT cells, FOXP4 downregulation also induced squamous differentiation via an ELF3\u2010dependent pathway. These findings suggest that downregulation of FOXP4 inhibits cell proliferation and promotes the differentiation of atypical cells in CIN lesions. Based on these results, we propose that FOXP4 is a novel target molecule for nonsurgical CIN treatment that inhibits CIN progression by inducing squamous differentiation.<\/jats:p>","DOI":"10.1111\/cas.15489","type":"journal-article","created":{"date-parts":[[2022,7,15]],"date-time":"2022-07-15T11:42:02Z","timestamp":1657885322000},"page":"3376-3389","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["<scp>FOXP4<\/scp> inhibits squamous differentiation of atypical cells in cervical intraepithelial neoplasia via an <scp>ELF3<\/scp>\u2010dependent pathway"],"prefix":"10.1111","volume":"113","author":[{"given":"Takeo","family":"Matsumoto","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Graduate School of Medical Sciences Kanazawa University  Kanazawa 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