miR-181a increases FoxO1 acetylation and promotes granulosa cell apoptosis via SIRT1 downregulation

• Published in: Cell death & disease 2017-10, Vol.8 (10), p.e3088-e3088
• Main Authors: Zhang, Mei, Zhang, Qun, Hu, Yali, Xu, Lu, Jiang, Yue, Zhang, Chunxue, Ding, Lijun, Jiang, Ruiwei, Sun, Jianxin, Sun, Haixiang, Yan, Guijun
• Format: Article
• Language: English
• Subjects: 3-Nitropropionic acid; 631/337/384/331; 631/80/458/1275; 631/80/82/23; 692/698/1460/1527/1710; Acetylation; Antibodies; Apoptosis; Apoptosis - drug effects; Apoptosis - genetics; Biochemistry; Cell Biology; Cell Culture; Deacetylation; Female; Forkhead Box Protein O1 - genetics; Forkhead protein; FOXO1 protein; Gene expression; Gene Expression Regulation - drug effects; Granulosa Cells - drug effects; Granulosa Cells - metabolism; Humans; Hydrogen peroxide; Hydrogen Peroxide - toxicity; Immunology; Life Sciences; MicroRNAs; MicroRNAs - genetics; Nitro Compounds - pharmacology; Original; original-article; Oxidative stress; Oxidative Stress - drug effects; Propionates - pharmacology; Signal Transduction - drug effects; SIRT1 protein; Sirtuin 1 - genetics; Transcription
• ISSN: 2041-4889; 2041-4889
• DOI: 10.1038/cddis.2017.467

Oxidative stress impairs follicular development by inducing granulosa cell (GC) apoptosis, which involves enhancement of the transcriptional activity of the pro-apoptotic factor Forkhead box O1 (FoxO1). However, the mechanism by which oxidative stress promotes FoxO1 activity is still unclear. Here, we found that miR-181a was upregulated in hydrogen peroxide (H 2 O 2 )-treated GCs and a 3-nitropropionic acid (NP)-induced in vivo model of ovarian oxidative stress. miR-181a overexpression promoted GC apoptosis, whereas knockdown of endogenous miR-181a blocked H 2 O 2 -induced cell apoptosis. Moreover, we identified that Sirtuin 1 (SIRT1), a deacetylase that suppresses FoxO1 acetylation in GCs, was downregulated by miR-181a and reversed the promoting effects of H 2 O 2 and miR-181a on FoxO1 acetylation and GC apoptosis. Importantly, decreased miR-181a expression in the in vivo ovarian oxidative stress model inhibited apoptosis by upregulating SIRT1 expression and FoxO1 deacetylation. Together, our results suggest that miR-181a mediates oxidative stress-induced FoxO1 acetylation and GC apoptosis by targeting SIRT1 both in vitro and in vivo .