Let-7e modulates the proliferation and the autophagy of human granulosa cells by suppressing p21 signaling pathway in polycystic ovary syndrome without hyperandrogenism

作者：Li, Ying; Liu, Yu-dong; Zhou, Xing-yu; Zhang, Jun; Wu, Xiao-min; Yang, Yi-zhen; Chen, Ying-xue; Zhang, Xiao-Fei; Li, Xin; Ma, Lin-zi; Wang, Zhe; Chen, Shi-ling^*

来源：Molecular and Cellular Endocrinology, 2021, 535: 111392.

DOI：10.1016/j.mce.2021.111392

• Let-7e
• Polycystic ovary syndrome (PCOS)
• Non-hyperandrogenic
• Granulosa cells
• Proliferation
• Autophagy

Polycystic ovary syndrome (PCOS) is a common endocrine and metabolic disorder in reproductive-aged women, and its pathogenesis is still under debate. Recent studies suggest crucial roles for microRNAs (miRNAs) in PCOS development. The let-7 family miRNAs constitute the most abundant miRNAs in human granulosa cells (GCs), and plays an important role in follicular development. However, research on the let-7e implications of the non-hyperandrogenic (non-HA) phenotype remains unclear. This study aimed at determining the role of let-7e in the progression of PCOS. We performed quantitative real-time PCR to examine the levels of let-7e in fifty-two non-HA PCOS patients and fifty-two controls. A receiver operating characteristic (ROC) curve were used to reveal the diagnostic value of let-7e in non-HA PCOS. Using an immortalized human granulosa cell line, KGN, we investigated the influence of let-7e on cell proliferation and autophagy. Our data substantiated the expression of let-7e was significantly increased in non-HA PCOS group, and associated with an increased antral follicle count. The ROC curve indicated a major separation between non-HA PCOS group and the control group. Let-7e knockdown suppressed cell proliferation and enhanced cell autophagy by activating p21 pathway. Conversely, let-7e over-expression promoted cell proliferation and inhibited cell autophagy by suppressing p21 pathway. Our results indicate that increased let-7e levels in non-HA PCOS GCs may contribute to excessive follicular activation and growth, thereby involving in the pathogenesis of PCOS. Let-7e may thus be a potential therapeutic target in non-HA PCOS.

• 单位
  南方医科大学