RRC ID 68106
Author Xu X, Song X, Xu X, Zheng Y, Xu L, Shen L.
Title Inhibition of sestrin 1 alleviates polycystic ovary syndrome by decreasing autophagy.
Journal Aging (Albany NY)
Abstract Polycystic ovary syndrome (PCOS) is the most common endocrine disorder in women of reproductive age, accounting for 50-70% of anovulatory infertility cases. However, the etiology of PCOS at the molecular level remains unclear. Here, bioinformatics analysis was performed to identify differentially expressed genes (DEGs) between adipose tissue of PCOS patients and matched tissues from non-hyperandrogenic women. RT-qPCR, western blot, cell counting kit-8 (CCK-8), EdU (5-Ethynyl-2'-deoxyuridine) staining, LC3 staining, ROS (reactive oxygen species) detection, and apoptosis assays were conducted to explore the effects of sestrin 1 on KGN human granulosa-like tumor cells. Bioinformatics analysis indicated that DEGs in adipose tissue from PCOS patients were enriched in the p53 signaling pathway. Moreover, sestrin 1 was identified as a major target of the p53 gene. Downregulation of sestrin 1 inhibited proliferation of KGN cells by inhibiting autophagy. Additionally, sestrin 1 downregulation increased ROS generation and promoted apoptosis in KGN cells. By contrast, overexpression of sestrin 1 increased cell viability by increasing autophagy in KGN cells. Together, these results suggest that downregulation of sestrin 1 may be a potential novel treatment strategy for PCOS.
Volume 13(8)
Pages 11774-11785
Published 2021-4-22
DOI 10.18632/aging.202872
PII 202872
PMID 33883304
PMC PMC8109134
MeSH Animals Apoptosis / genetics Autophagy / genetics* Case-Control Studies Cell Cycle Proteins / genetics* Cell Line, Tumor Computational Biology Datasets as Topic Disease Models, Animal Female Gene Expression Profiling Gene Knockdown Techniques Granulosa Cells / pathology Healthy Volunteers Heat-Shock Proteins / genetics* Humans Intra-Abdominal Fat / pathology* Omentum Polycystic Ovary Syndrome / genetics* Polycystic Ovary Syndrome / pathology Rats Reactive Oxygen Species Tumor Suppressor Protein p53 / metabolism Up-Regulation
IF 4.831
Human and Animal Cells KGN(RCB1154)