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• W4289526097 abstract "Polycystic ovary syndrome (PCOS) is a common endocrine disorder of unknown etiology that occurs in women of reproductive age. Despite being considered to affect up to one-fifth of women in this cohort, the condition lacks generally accepted diagnostic biomarkers and options for targeted therapy. Hereby, we analyzed the diagnostic, therapeutic, and functional potential of a recently discovered miR-335-5p that was observed to be reduced in the follicular fluid (FF) of PCOS patients as compared with healthy women. We found miR-335-5p to be significantly decreased in the serum and FF samples of PCOS patients (n = 40) vs healthy women (n = 30), as well as in primary human granulosa cells (hGCs), and in 3 different hormonally induced PCOS-like murine models vs. wild-type (WT) mice. The level of circulating miR-335-5p was found to significantly correlate with the impaired endocrine and clinical features associated with PCOS in human patients. Ovarian intrabursal injection of the miR-335-5p antagomir in WT mice ovaries induced a PCOS-like reproductive phenotype. Treatment with the miR-335-5p agomir rescued the dihydrotestosterone-induced PCOS-phenotype in mice, thereby providing a functional link between miR-335-5p and PCOS. We identified SP1 as a miR-335-5p target gene by using the dual-luciferase reporter assay. Both the luciferase reporter assay and chromatin immunoprecipitation assay showed that SP1 bound to the promoter region of human CYP19A1 and inhibited its transcription. miR-335-5p increased the production of estradiol via the SP1/CYP19A1 axis in hGCs, thereby suggesting its mechanistic pathway of action. In conclusion, these results provide evidence that miR-335-5p may function as a mediator in the etiopathogenesis of PCOS, as well as has the potential as both a novel diagnostic biomarker and therapeutic target for PCOS." @default.
• W4289526097 created "2022-08-03" @default.
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• W4289526097 date "2023-02-01" @default.
• W4289526097 modified "2023-10-11" @default.
• W4289526097 title "Role and mechanism of miR-335-5p in the pathogenesis and treatment of polycystic ovary syndrome" @default.
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• W4289526097 doi "https://doi.org/10.1016/j.trsl.2022.07.007" @default.
• W4289526097 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35931409" @default.
• W4289526097 hasPublicationYear "2023" @default.
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