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Selenoprotein I (SELENOI) is a crucial mediator implicated in human hereditary spastic paraplegia. However, its role in human tumors remains poorly elucidated. Here, we comprehensively analyzed SELENOI expression patterns, functions, and clinical implications across various malignancies through the integration of bulk transcriptomics, cancer databases, and in vitro and in vivo experiments. Pan\u2010cancer analysis indicated upregulated SELENOI expression across various cancers, correlating with augmented malignancy, suppressed tumor immunity and poor prognosis. Knockdown of <jats:italic>SELENOI<\/jats:italic> caused G0\/G1\u2010phase cell cycle arrest and diminished aggressive cancer phenotypes in OV cells. Moreover, SELENOI inhibition augments ferroptosis and reverses the cisplatin resistance in OV cells by modulating Akt phosphorylation. Conversely, overexpression of <jats:italic>SELENOI<\/jats:italic> in OV cells enhanced therapeutic sensitivity to cisplatin by upregulating Akt phosphorylation. Importantly, in vivo studies demonstrated that SELENOI inhibition suppressed ovarian tumor growth and enhanced cisplatin's anticancer effects. These findings highlight the significant role of SELENOI in OV by modulating ferroptosis and chemotherapy resistance. Targeting SELENOI represents a promising therapeutic approach to promote the efficacy of platinum\u2010based chemotherapy in OV, particularly in cases of resistance.<\/jats:p>","DOI":"10.1002\/mco2.70033","type":"journal-article","created":{"date-parts":[[2024,12,12]],"date-time":"2024-12-12T07:16:22Z","timestamp":1733987782000},"source":"Crossref","is-referenced-by-count":7,"title":["Inhibition of Selenoprotein I promotes ferroptosis and reverses resistance to platinum chemotherapy by impairing Akt phosphorylation in ovarian cancer"],"prefix":"10.1002","volume":"5","author":[{"given":"Jing","family":"Li","sequence":"first","affiliation":[{"name":"Department of Gynecology Shenzhen Second People's Hospital the First Affiliated Hospital of Shenzhen University Shenzhen China"},{"name":"Guangdong Key Laboratory for Biomedical Measurements and Ultrasound Imaging National\u2010Regional Key Technology Engineering Laboratory for Medical Ultrasound School of Biomedical Engineering Shenzhen University Medical School Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mimi","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shenzhen Second People's Hospital the First Affiliated Hospital of Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dingwen","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shenzhen Second People's Hospital the First Affiliated Hospital of Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shenzhen Second People's Hospital the First Affiliated Hospital of Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shenzhen Second People's Hospital the First Affiliated Hospital of Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhua","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shenzhen Second People's Hospital the First Affiliated Hospital of Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanqun","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Gynecology Shenzhen Second People's Hospital the First Affiliated Hospital of Shenzhen University Shenzhen China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhili","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Endocrinology and Metabolism Nanfang Hospital Southern Medical University Guangzhou 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