MiR-23a induced the activation of CDC42/PAK1 pathway and cell cycle arrest in human cov434 cells by targeting FGD4

Ji Lin,Jianfen Huang,Liheng Lin,Weiwei Li,Huijuan Huang

doi:10.1186/s13048-020-00686-9

Abstract

BackgroundMiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. In the present study, we investigated the specific role of miR-23a in cov434 cells.ResultsDownregulation of miR-23a was observed in serum of PCOS patients compared with the healthy control, suggesting the inhibitory effect of miR-23a in PCOS. MiR-23a was positively correlated with Body Mass Index (BMI) and negatively correlated with Luteinizing hormone (LH), Testostrone (T), Glucose (Glu) and Insulin (INS) of PCOS patients. MiR-23a mimic inhibited the proliferation and promoted apoptosis of human cov434 cells. In addition, flow cytometry assay confirmed that miR-23a blocked cell cycle on G0/G1 phase. MiR-23a inhibitor showed opposite results. Furthermore, double luciferase reporter assay proved that miR-23a could bind to the 3’UTR of FGD4 directly through sites predicted on Target Scan. FGD4 level was significantly suppressed by miR-23a mimic, but was significantly enhanced by miR-23a inhibitor. We further proved that miR-23a increased the expression of activated CDC42 (GTP bround) and p-PAK-1, suggesting that miR-23a induced cell cycle arrest through CDC42/PAK1 pathway.ConclusionsIn conclusion, our study reveals that miR-23a participates in the regulation of proliferation and apoptosis of cov434 cells through target FGD4, and may play a role in the pathophysiology of PCOS.

Highlights

MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation
MiR-23a was downregulated in serum of Polycystic ovary syndrome (PCOS) patients Peripheral blood was collected from 50 local PCOS patients for the detection of miR-23a level with 50 healthy women’s peripheral blood as the control
In this study, we explored the differences in serum levels of miR-23a between PCOS patients and normal women, as well as the effects of miR-23a on biological behavior such as proliferation and apoptosis of cov434 cells and related specific molecular mechanisms, in order to provide limited theoretical support and experimental data for the application of miRNA in PCOS treatment

Summary

Introduction

MiRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation. Polycystic ovary syndrome (PCOS) is the most common reproductive, endocrine and metabolic disorder disease in women, characterized by ovulation disorders, hyperandrogenism and insulin resistance [1, 2]. PCOS affects about 5– 10% of women of childbearing age, accounting for 75% of anovulatory infertility, and usually a lifelong disease. Women with PCOS have an increased risk of insulin resistance, hypertension, type 2. The role of microRNAs (miRNAs) in ovarian physiology and pathology has attracted much attention. Some studies have shown that miRNAs play important roles in the development of ovarian cancer, activation of primitive follicles, follicular development, oocyte maturation and ovulation [6,7,8].

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