Abstract
Objective The abnormal expression of LncRNA H19 and miR-140-5p has been linked to ovarian cancer (OC). Whether H19 directly regulates miR-140-5p in ovarian cancer cells has been unclear. In this study, we deeply explored the relationship between H19 and miR-140-5p in ovarian cancer and the mechanism of action in regulating OC progression. Methods A total of 66 patients with OC admitted to the hospital from June 2017 to June 2019 were selected as the research group (RG), and meanwhile, 60 cases of healthy subjects were selected as the control group (CG). In addition, OC cells and normal ovarian epithelial cells were used to detect H19 and miR-140-5p expression levels and to analyze the effect of H19 on OC cells. The activation of the PI3K/AKT pathway and downstream proteins were analyzed by western blot. Results H19 was highly expressed while miR-140-5p was lowly expressed in OC patients and cell lines (P < 0.050). The proliferation, invasion, migration ability, and epithelial-mesenchymal transition (EMT) of OC cells were reduced after inhibiting H19 expression, and the apoptosis rate was increased. Transfection of cells with miR-140-5p mimics brought opposite effects. Online prediction and dual-luciferase reporter (DLR) confirmed that H19 directly binds miR-140-5p. Western blot assay indicated overexpression activated the PI3K/AKT signaling pathway in OC cells. Moreover, overexpression promoted tumor growth in nude mice and was suppressed by PI3K inhibitor. Conclusion LncRNA H19 downregulation of miR-140-5p to activate the PI3K/AKT signaling pathway and promote the proliferation, invasion, migration and EMT of OC.
Highlights
Ovarian cancer (OC) is currently one of the most frequently occurring tumors worldwide, accounting for approximately4% of all female systemic malignancies [1]
LncRNA H19 has been found to be abnormally expressed in human malignant tumors and regulates cell proliferation, migration, invasion, antiapoptosis, and epithelial-mesenchymal transition (EMT) through various mechanisms, playing a carcinogenic or anticancer role [5,6,7]
We found that overexpression of H19 in ovarian cancer cells downregulated miR-140-5p and promoted invasion, migration, and epithelial-mesenchymal transition of ovarian cancer cells by the activation of the PI3K/AKT signaling pathway
Summary
Ovarian cancer (OC) is currently one of the most frequently occurring tumors worldwide, accounting for approximately4% of all female systemic malignancies [1]. LncRNA H19 has been found to be abnormally expressed in human malignant tumors and regulates cell proliferation, migration, invasion, antiapoptosis, and epithelial-mesenchymal transition (EMT) through various mechanisms, playing a carcinogenic or anticancer role [5,6,7]. Overexpression of H19 has been linked to the cisplatin resistance and migration of ovarian cancer during EMT [13, 14]. It acted as a competing endogenous RNA of miR-370-3p to promote EMT of ovarian cancer cells [15]. H19 promotes small cell lung cancer (SCLC) progression via sponging miR-140-5p [16]
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