ABSTRACT
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.
ABSTRACT
BACKGROUND: Recently, long non-coding RNAs (lncRNAs) were considered as important gene expression regulators involving various biological processes. In this study, we explored the role of lncRNAs in the pathogenesis of radiation-induced intestinal fibrosis (RIF). METHODS: LncRNAs were screened by microarray (Human LncRNA Array v3.0, Arraystar, Inc.) and the differentially expressed lncRNAs in RIF and non-RIF were analyzed by bioinformatics methods. The expression of WWC2-AS1/miR-16/FGF2 axis was compared on mRNA and protein level between human intestinal CCD-18Co fibroblasts cell lines and subepithelial SEMFs in response to radiation treatment. The significance of WWC2-AS1 in regulating FGF2 associated proliferation, migration, invasion and fibrosis of CCD-18Co and SEMFs by exposure to radiation was analyzed by shRNA (WWC2-AS1 shRNA) knock-down of endogenous WWC2-AS1. RESULTS: WWC2-AS1 and FGF2 level was significantly higher while miR-16 was down-regulated in radiation-treated intestinal tissues. WWC2-AS1 more potently boosted FGF2 expression via reducing miR-16, and WWC2-AS1 shRNA remarkably inhibited FGF2 associated proliferation, migration, invasion and fibrosis of radiation treatment in vitro, further demonstrating physical interaction between miR-16 and WWC2-AS1 in radiation-induced fibrosis progress. CONCLUSIONS: WWC2-AS1 was highly expressed in RIF, may function as a ceRNA in the regulation of FGF2 by binding miR-16. Targeting WWC2-AS1 thus may benefit radiation-induced fibrosis treatment.
