Department of Obstetrics and Gynecology, The First Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong 515041, China.
Department of Microbiology and Immunology, Shantou University Medical College, Shantou, Guangdong 515041, China.
Aging (Albany NY). 2021 Apr 22;13(8):11774-11785. doi: 10.18632/aging.202872.
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.
多囊卵巢综合征（PCOS）是育龄妇女中最常见的内分泌紊乱疾病，占无排卵性不孕病例的 50-70%。然而，PCOS 在分子水平上的病因仍然不清楚。在这里，我们进行了生物信息学分析，以鉴定多囊卵巢综合征患者脂肪组织与非高雄性激素女性匹配组织之间的差异表达基因（DEGs）。通过实时定量 PCR（RT-qPCR）、Western blot、细胞计数试剂盒-8（CCK-8）、EdU（5-乙炔基-2'-脱氧尿苷）染色、LC3 染色、ROS（活性氧）检测和凋亡实验，研究 sestrin 1 对 KGN 人卵巢颗粒样肿瘤细胞的影响。生物信息学分析表明，PCOS 患者脂肪组织中的 DEGs 富集于 p53 信号通路。此外，sestrin 1 被鉴定为 p53 基因的主要靶标。下调 sestrin 1 可通过抑制自噬来抑制 KGN 细胞的增殖。此外，下调 sestrin 1 会增加 KGN 细胞中 ROS 的产生并促进细胞凋亡。相比之下，过表达 sestrin 1 通过增加 KGN 细胞中的自噬来提高细胞活力。总之，这些结果表明下调 sestrin 1 可能是 PCOS 的一种潜在的新型治疗策略。
