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Downregulated lncRNA NEAT1 Upregulates microRNA-381 to Induce Proliferation and Repress Apoptosis of Ovarian Granulosa Cells in Polycystic Ovarian Syndrome Rats by Inhibiting IGF1 Expression
34 Pages Posted: 17 Jul 2020
More...Abstract
Objective: To date, some researchers have revealed the participation of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovarian syndrome (PCOS), but none of them has mentioned the roles of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 in PCOS. Hence, this study is carried out to understand the role of NEAT1/miR-381/insulin-like growth factor 1 (IGF1) axis in PCOS.
Methods: Firstly, dehydroepiandrosterone-induced PCOS rat model was established. Then, NEAT1, miR-381 and IGF1 expression in ovarian tissues and ovarian granulosa cells of PCOS rats was detected. Furthermore, estradiol (E2) and progesterone (P4) expression levels were determined. Next, the ovarian granulosa cells were introduced with NEAT1-siRNA or miR-381 mimics to figure out theirs functions in ovarian granulosa cell proliferation and apoptosis. Finally, the binding relationships between NEAT1 and miR-381 as well as between miR-381 and IGF1 were verified.
Results: High expression of lncRNA NEAT1 and IGF1 and low expression of miR-381 were found in ovarian tissues and ovarian granulosa cells of PCOS rats. Silenced NEAT1 promoted E2 and P4 expression in PCOS rats. Silenced NEAT1 elevated miR-381 to promote proliferation and repress apoptosis of ovarian granulosa cells in PCOS rats. LncRNA NEAT1 acted as a competing endogenous RNA to adsorb miR-381, and IGF1 was verified to be a direct target gene of miR-381.
Conclusion: Our study provides evidence that downregulation of NEAT1 upregulated miR-381 to promote proliferation and inhibit apoptosis of ovarian granulosa cells in PCOS rats by inhibiting IGF1.
Funding Statement: None.
Declaration of Interests: The authors declare that they have no conflicts of interest.
Ethics Approval Statement: The study was agreed by the Animal Ethics Committee of Peking Union Medical College Hospital. All animal experiments were in line with the Guide for the Care and Use of Laboratory Animal by International Committees.
Keywords: Polycystic ovarian syndrome; Long non-coding RNA nuclear-enriched abundant transcript 1; MicroRNA-381; Insulin-like growth factor 1; Ovarian granulosa cells; Apoptosis; Proliferation
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