miR-455-3p inhibits proliferation, migration and epithelial-mesenchymal transition of ovarian cancer SKOV-3 cells by regulating translipoprotein 4 / 中国肿瘤生物治疗杂志

ABSTRACT

@#Objective: To investigate the potential effects of miR-455-3p on proliferation, invasion and epithelial-mesenchymal transition (EMT) process of ovarian cancer cells, and explore its molecular mechanism. Methods: The IOSE80, SKOV-3 and A2780 cells were transfected with miR-455-3p mimics and negative controls (NC) by using LipofectamineTM 2000. Quantitative polymerase chain reaction (qPCR) assay was performed to detect the mRNA expressions of miR-455-3p and fatty acid-binding protein 4 (FABP4) in IOSE80, SKOV-3 and A2780 cells. The expression levels of FABP4 and EMT-associated proteins were detected by Wb. CCK-8 assay was applied to measure cell proliferation. Cell migration was analyzed by using Transwell assay. Bioinformatics analysis was used to predict the potential target of miR-455-3p, and the targeting effect of miR-455-3p on FABP4 was verified by the dual-luciferase reporter assay system. Results: The expression of miR-455-3p was declined (all P<0.05), while the expression of FABP4 was elevated (all P< 0.05) in ovarian cancer cells (SKOV-3 and A2780) in comparison with normal ovarian IOSE80 cells. Additionally, over-expression of miR-455-3p obviously inhibited cell proliferation and migration capacity of SKOV-3 cells (all P<0.05). Furthermore, over-expression of miR-455-3p impeded EMT progress by up-regulating E-cadherin expression and down-regulating N-cadherin and vimentin expression (all P<0.05). Importantly, the dual-luciferase reporter system, qPCR and Wb validated that FABP4 was a specific target gene of miR-455-3p, and miR-455-3p showed specific binding with FABP4 3’-UTR and negatively regulated the expression of FABP4 at both mRNA and protein levels. Mechanistically, over-expression of FABP4 apparently reversed the inhibitory effects of miR-455-3p on cell proliferation and migration of SKOV-3 cells (all P<0.05). Conclusion: miR-455-3p, acting as a tumor suppressor protein, can inhibit ovarian cancer cell proliferation, migration and EMT process by targeting FABP4, suggesting that miR-455-3p may be a new potential therapeutic target for ovarian cancer treatment.