MicroRNA-194 is increased in polycystic ovary syndrome granulosa cell and induce KGN cells apoptosis by direct targeting heparin-binding EGF-like growth factor

Yi-Xuan Wu,Yan-Shan Lin,Mingwei Cheng,Si-Chen Li,Hai-Ying Liu,Lin Zhu,Xi Yao

doi:10.1186/s12958-021-00850-w

Abstract

BackgroundPolycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility. Abnormal proliferation and apoptosis of granulosa cells (GCs) are thought to be the critical factors leading to abnormal maturation of follicles. It has been shown that microRNAs (miRNAs) exert a significant influence in the pathogenesis of PCOS; however, the relationship between miRNA, PCOS, and GC apoptosis is not entirely understood.MethodsTo clarify the effect of miR-194 in PCOS, CCK-8, Ki67 staining, AO/EB, and flow cytometry assays were used to assess cell growth, proliferation, and apoptosis in KGN cells, which were artificially stimulated to overexpress miR-194. Luciferase reporter assays and rescue experiments were used to elucidate the mechanism underlying miR-194 in PCOS.ResultsmiR-194 expression was significantly up-regulated in rat models of PCOS and the ovarian GCs of PCOS patients. miR-194 suppression promoted KGN cell growth and proliferation. miR-194 overexpression also induced cell apoptosis, while miR-194 downregulation had an opposite effect. Furthermore, up-regulating heparin-binding EGF-like growth factor (HB-EGF) expression rescued the pro-apoptotic effects of miR-194 upregulation on KGN cells.ConclusionsmiR-194 is increased in PCOS granulosa cell and mayfunction as a novel biomarker and therapeutic target for KGN cells via HB-EGFregulation.

Highlights

Polycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility
MiR-103 has likely been associated with PCOS through its effect on IRS1 and subsequent modulation of the PI3K/AKT signaling pathway [13]. These findings showed that miRNAs are well-established in post-transcriptional regulation involved in PCOSrelated molecular expression and granulosa cells (GCs) apoptosis in PCOS
Results miR‐194 expression was up‐regulated in PCOS GCs miR-194 expression was up-regulated in the GCs of PCOS patients in contrast to the normal group as shown by qRT-PCR (Fig. 1 A)

Summary

Introduction

Polycystic ovary syndrome (PCOS) is an endocrine-related follicular developmental disorder that affects 50 %-70 % of reproductive-aged women diagnosed with ovulation-related infertility. Abnormal proliferation and apoptosis of granulosa cells (GCs) are thought to be the critical factors leading to abnormal maturation of follicles. Polycystic ovary syndrome (PCOS) is an endocrine disorder that affects female fertility. Studies have demonstrated that FSH promotes granulosa cell (GC) proliferation and differentiation [4]. Follicular atresia is a significant cause of female infertility. This phenomenon is closely related to ovarian follicle development and GC apoptosis, and GC apoptosis is thought to be the primary mechanism underlying follicular atresia.

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Conclusion