Long noncoding RNA H19 promotes transforming growth factor-β-induced epithelial–mesenchymal transition by acting as a competing endogenous RNA of miR-370-3p in ovarian cancer cells

Abstract

Jing Li, YingYing Huang, XiaoJun Deng, ManLing Luo, XueFei Wang, HaiYan Hu, CiDi Liu, Mei Zhong Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, People’s Republic of China Abstract: Ovarian cancer is a gynecological malignant tumor with a high mortality rate among women, owing to metastatic progression and recurrence. Acquisition of invasiveness is accompanied by the loss of epithelial features and a gain of a mesenchymal phenotype, a process known as epithelial–mesenchymal transition (EMT). Transforming growth factor-β (TGF-β) has been implicated in the regulation of EMT. In the present study, we aimed to investigate the role of long noncoding RNA H19 and microRNA-370 (miR-370-3p) in TGF-β-induced EMT. Ovarian cancer cell lines SKOV-3 and OVCAR3 were incubated with different concentrations of TGF-β, and the results showed that TGF-β treatment upregulated H19 and downregulated miR-370-3p. In addition, an H19 knockdown or miR-370-3p overexpression suppressed TGF-β-induced EMT, while H19 overexpression or a miR-370-3p knockdown promoted TGF-β-induced EMT. Mechanistically, H19 could directly bind to miR-370-3p and effectively act as its competing endogenous RNA. Furthermore, we demonstrated that this activity of H19 was involved in its promotion of TGF-β-induced EMT. Thus, our results may provide novel insights into the process of TGF-β-induced EMT. Keywords: transforming growth factor-β, long noncoding RNA H19, microRNA-370-3p, competing endogenous RNA, epithelial–mesenchymal transition

Keywords

• transforming growth factor β
• long noncoding RNA H19
• microRNA-370-3p
• competing endogenous RNA
• epithelial-mesenchymal transition