Abstract
BackgroundPolycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. The mechanism by which circular RNA (circRNA) drives PCOS development remains unclear. Thus, the study is designed to explore the role of a novel circRNA, circ_FURIN, in the PCOS cell model and the underlying mechanism.MethodsPCOS cell model was established by treating human ovarian granulosa-like tumor cells (KGN) with Testosterone (TTR). RNA expressions of circ_FURIN, microRNA-423-5p (miR-423-5p) and myotubularin 1 (MTM1) were detected by quantitative real-time polymerase chain reaction (qRT-PCR). Protein expression was checked by Western blot. Cell proliferation was investigated by a 5-Ethynyl-29-deoxyuridine assay, 3-(4,5-Dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and flow cytometry analysis for cell cycle. Apoptotic cells were quantified by flow cytometry analysis for cell apoptosis. The interplay between miR-423-5p and circ_FURIN or MTM1 was identified by dual-luciferase reporter and RNA pull-down assays.ResultsCirc_FURIN and MTM1 expressions were significantly upregulated, whereas miR-423-5p was downregulated in the ovarian cortex tissues of PCOS patients and TTR-treated KGN cells compared with controls. Circ_FURIN depletion relieved TTR-induced proliferation inhibition and apoptosis promotion. Besides, knockdown of miR-423-5p, a target miRNA of circ_FURIN, rescued circ_FURIN knockdown-mediated effects under TTR treatment. MiR-423-5p remitted TTR-induced cell disorders by binding to MTM1. Moreover, circ_FURIN modulated MTM1 expression through miR-423-5p.ConclusionCirc_FURIN silencing protected against TTR-induced dysfunction by the miR-423-5p/MTM1 pathway in human ovarian granulosa-like tumor cells.
Highlights
Polycystic ovary syndrome (PCOS) is a metabolic endocrinopathy that is the most leading cause for anovulatory infertility, featured by menstrual irregularity, hyperandrogenism and polycystic ovaries [1]
We investigated whether the circ_FURIN/miR-423-5p/MTM1 pathway was required for PCOS progression
Circ_FURIN expression was upregulated in ovarian cortex tissues of PCOS patients Circ_FURIN, named circ_0036881, is looped and comprised of the exon 16 of FURIN gene, and its headto-tail splicing was confirmed by Sanger sequencing (Fig. 1A)
Summary
Polycystic ovary syndrome (PCOS) is a metabolic endocrinopathy that is the most leading cause for anovulatory infertility, featured by menstrual irregularity, hyperandrogenism and polycystic ovaries [1]. The abnormal development of follicular in follicular fluid is considered a vital feature of PCOS [3]. A previous reference has expounded that granulosa cells can secrete the major components of follicular fluid [4]. An in-depth investigation of the molecular mechanism of PCOS development using granulosa cells can provide a direction for identifying the molecular target of the disease. Polycystic ovary syndrome (PCOS) is a common endocrine disorder among reproductive-age women. The mechanism by which circular RNA (circRNA) drives PCOS development remains unclear. The study is designed to explore the role of a novel circRNA, circ_FURIN, in the PCOS cell model and the underlying mechanism
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