TY - JOUR
T1 - The selenoenzyme type I iodothyronine deiodinase
T2 - a new tumor suppressor in ovarian cancer
AU - Alfandari, Adi
AU - Moskovich, Dotan
AU - Weisz, Avivit
AU - Katzav, Aviva
AU - Kidron, Debora
AU - Beiner, Mario
AU - Josephy, Dana
AU - Asali, Aula
AU - Hants, Yael
AU - Yagur, Yael
AU - Weitzner, Omer
AU - Ellis, Martin
AU - Itchaki, Gilad
AU - Ashur-Fabian, Osnat
N1 - Publisher Copyright:
© 2024 The Authors. Molecular Oncology published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.
PY - 2024
Y1 - 2024
N2 - 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-grade serous ovarian carcinoma (HGSOC), the most lethal gynecologic cancer. We studied DIO1 expression in HGSOC patients [The Cancer Genome Atlas (TCGA) data and tumor tissues], human cell lines (ES-2 and Kuramochi), normal Chinese hamster ovarian cells (CHO-K1), and normal human fallopian tube cells (FT282 and FT109). To study its functional role, DIO1 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 DIO1 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 DIO1 ectopic expression. Proteomics analysis in DIO1-KD 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.
AB - 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-grade serous ovarian carcinoma (HGSOC), the most lethal gynecologic cancer. We studied DIO1 expression in HGSOC patients [The Cancer Genome Atlas (TCGA) data and tumor tissues], human cell lines (ES-2 and Kuramochi), normal Chinese hamster ovarian cells (CHO-K1), and normal human fallopian tube cells (FT282 and FT109). To study its functional role, DIO1 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 DIO1 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 DIO1 ectopic expression. Proteomics analysis in DIO1-KD 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.
KW - deiodinase
KW - expression
KW - gene silencing
KW - ovarian cancer
KW - proliferation
UR - http://www.scopus.com/inward/record.url?scp=85186890054&partnerID=8YFLogxK
U2 - 10.1002/1878-0261.13612
DO - 10.1002/1878-0261.13612
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C2 - 38429887
AN - SCOPUS:85186890054
SN - 1574-7891
JO - Molecular Oncology
JF - Molecular Oncology
ER -