{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,3]],"date-time":"2026-03-03T22:39:01Z","timestamp":1772577541547,"version":"3.50.1"},"reference-count":63,"publisher":"Wiley","license":[{"start":{"date-parts":[[2024,3,1]],"date-time":"2024-03-01T00:00:00Z","timestamp":1709251200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100011600","name":"Cancer Biology Research Center, Tel Aviv University","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100011600","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Molecular Oncology"],"abstract":"<jats:p>The selenoenzyme type I iodothyronine deiodinase (DIO1) catalyzes removal of iodine atoms from thyroid hormones. Although DIO1 action is reported to be disturbed in several malignancies, no work has been conducted in high\u2010grade serous ovarian carcinoma (HGSOC), the most lethal gynecologic cancer. We studied <jats:italic>DIO1<\/jats:italic> expression in HGSOC patients [The Cancer Genome Atlas (TCGA) data and tumor tissues], human cell lines (ES\u20102 and Kuramochi), normal Chinese hamster ovarian cells (CHO\u2010K1), and normal human fallopian tube cells (FT282 and FT109). To study its functional role, <jats:italic>DIO1<\/jats:italic> was overexpressed, inhibited [by propylthiouracil (PTU)], or knocked down (KD), and cell count, proliferation, apoptosis, cell viability, and proteomics analysis were performed. Lower DIO1 levels were observed in HGSOC compared to normal cells and tissues. TCGA analyses confirmed that low <jats:italic>DIO1<\/jats:italic> mRNA expression correlated with worse survival and therapy resistance in patients. Silencing or inhibiting the enzyme led to enhanced ovarian cancer proliferation, while an opposite effect was shown following <jats:italic>DIO1<\/jats:italic> ectopic expression. Proteomics analysis in <jats:italic>DIO1<\/jats:italic>\u2010KD cells revealed global changes in proteins that facilitate tumor metabolism and progression. In conclusion, DIO1 expression and ovarian cancer progression are inversely correlated, highlighting a tumor suppressive role for this enzyme and its potential use as a biomarker in this disease.<\/jats:p>","DOI":"10.1002\/1878-0261.13612","type":"journal-article","created":{"date-parts":[[2024,3,2]],"date-time":"2024-03-02T05:39:43Z","timestamp":1709357983000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["The selenoenzyme type I iodothyronine deiodinase: a new tumor suppressor in ovarian cancer"],"prefix":"10.1002","author":[{"given":"Adi","family":"Alfandari","sequence":"first","affiliation":[{"name":"Translational Oncology Laboratory Hematology Institute, Meir Medical Center  Kfar Saba Israel"},{"name":"Department of Human Molecular Genetics and Biochemistry, Faculty of Medicine Tel Aviv University  Israel"},{"name":"School of Medicine, Faculty of Medical and Health Sciences Tel Aviv University  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