WWC2-AS1/miR-382-5p/FZD3轴调控多囊卵巢综合征卵巢颗粒细胞增殖、凋亡

WWC2-AS1/miR-382-5p/FZD3 axis regulates proliferation and apoptosis of ovarian granulosa cells in polycystic ovary syndrome

目的本研究旨在探讨WWC2-AS1/miR-382-5p/FZD3在多囊卵巢综合征(polycystic ovarian syndrome,PCOS)患者颗粒细胞(GCs)中的作用及其分子机制。方法借助生物信息学工具预测PCOS中的分子机制。采用qRT-PCR检测PCOS患者及对照组的血清和GCs中WWC2-AS1、miR-382-5p和FZD3的表达。CCK-8和流式细胞术观察WWC2-AS1/miR-382-5p/FZD3对GCs增殖和凋亡的影响。双荧光素酶报告实验验证WWC2-AS1和miR-382-5p、miR-382-5p和FZD3的互作用关系。结果与对照组相比,PCOS患者的血清和GCs中WWC2-AS1和FZD3表达显著上调,miR-382-5p表达下调(均P<0.05)。沉默WWC2-AS1能显著促进PCOS中的GCs增殖,抑制GCs凋亡(均P<0.05)。PCOS中存在WWC2-AS1/miR-382-5p/FZD3互作用网络,miR-382-5p抑制剂或过表达FZD3均可部分逆转沉默WWC2-AS1对PCOS中GCs的调控作用(均P<0.05)。结论本研究表明WWC2-AS1调控miR-382-5p上调FZD3在PCOS进展中促进GCs增殖,抑制细胞凋亡。WWC2-AS1/miR-382-5p/FZD3可能是治疗PCOS的有效分子靶点。

Objective To investigate the role of WWC2-AS1/miR-382-5p/FZD3 in granulosa cell(GCs)of polycystic ovary syndrome(polycystic ovarian syndrome,PCOS)patients and its molecular mechanism.Methods Bioinformatics tools were used to predict the molecular mechanism of PCOS.The expressions of WWC2-AS1,miR-382-5p and FZD3 in serum and GCs of patients with PCOS and healthy controls were detected by qRT-PCR.The effects of WWC2-AS1/miR-382-5p/FZD3 on the proliferation and apoptosis of GCs were observed by CCK-8 and flow cytometry.The interaction between WWC2-AS1 and miR-382-5p,miR-382-5p and FZD3 was verified by double luciferase report experiment.Results Compared with the control group,the expression of WWC2-AS1 and FZD3 in serum and GCs of PCOS patients was significantly up-regulated,while the expression of miR-382-5p was down-regulated.Silencing WWC2-AS1 could significantly promote the proliferation of GCs in PCOS and inhibit the apoptosis of GCs(all P<0.05).There is a WWC2-AS1/miR-382-5p/FZD3 interaction network in PCOS,and miR-382-5p inhibitor or overexpressed FZD3 can partially reverse the regulatory effect of silent WWC2-AS1 on GCs in PCOS.Conclusion This study shows that WWC2-AS1 regulates miR-382-5p and up-regulates FZD3,which promotes the proliferation of GCs and inhibits apoptosis in the progression of PCOS.WWC2-AS1/miR-382-5p/FZD3 may be an effective molecular target for the treatment of PCOS.