MicroRNA-489 targets XIAP to inhibit the biological progression of ovarian cancer via regulating PI3K/Akt signaling pathway and epithelial-to-mesenchymal transition.

Abstract

Ovarian cancer (OC) is a deathful malignant tumor in women worldwide, and its poor prognosis mainly results from metastasis. Recently, microRNA (miRNA/miR) has been found to exert crucial functions in the progression of multiple tumors by affecting expressions of their targets. However, the biological roles and the potential mechanism of miR-489 in OC need further elucidation. Quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) was utilized to confirm the miR-489 expressions in OC tissue samples and cell lines. The functions of miR-489 were analyzed by performing functional assays, such as MTT (3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assays and transwell assays. The downstream target of miR-489 was confirmed by TargetScan and luciferase reporter assay. Western blot was conducted to detect the expression of indicators associated with the down-stream signaling pathway. MiR-489 was prominently downregulated in OC tissues and cells, and the decreased miR-489 expression was related to malignant clinicopathologic features and poor prognosis of OC patients. Functional assays demonstrated that miR-489 could suppress OC cell viability, invasion, and migration. X-linked inhibitor of apoptosis protein (XIAP) was identified as a target of miR-489 and partially regulated the functions of miR-489 in OC. Moreover, we found that miR-489 inhibits OC progression via regulating phosphatidyl-inositol 3-kinase/protein kinase B pathway (PI3K/AKT) and epithelial-to-mesenchymal transition (EMT). Our results demonstrated that miR-489 inhibited OC development by directly binding to XIAP and regulating PI3K/Akt and EMT signal pathways, and miR-489 might serve as a promising biomarker for OC treatment in the future.