Re-expression of microRNA-4319 inhibits growth of prostate cancer via Her-2 suppression

Abstract

Purpose: Her-2 is an epidermal growth factor receptor expressed in some prostate cancers (PC) associated with outgrowth of the tumor. Dysregulation of some microRNAs is involved in the regulation of PC pathogenesis, whereas the role of miR-4319 in PC is unknown and addressed in the current study. Methods: The levels of miR-4319 in PC tissues were determined by RT-qPCR and their association with patient survival was studied by Kaplan–Meier analysis. Targeted genes for miR-4319 were predicted by a bioinformatics algorithm and confirmed by a dual-luciferase reporter assay. Growth of cells of overexpression or inhibition of miR-4319 or Her-2 was analyzed by an MTT assay. Cell survival in response to a chemotherapeutic drug, estramustine (EM), was analyzed by CCK-8 assay. Cell apoptosis was evaluated by TUNEL assay and Western blotting for apoptosis-associated proteins. Results: MiR-4319 levels were decreased in PC specimens, compared to corresponding normal prostate tissue. Lower levels of miR-4319 were correlated with poorer overall patients’ survival. In vitro, the cell survival mediated with Her-2 against chemotherapy was inhibited by overexpression of miR-4319 and was enhanced by depletion of miR-4319. Depletion of miR-4319 in primary prostate epithelial cells increased Her-2-dependent cell growth, while re-expression of miR-4319 in PC cells inhibited Her-2-dependent cell growth and Her-2-dependent resistance to EM-induced apoptosis. Conclusion: The growth and chemo-resistance of PC cells may be suppressed via re-expression of miR-4319 that inhibits Her-2 signaling.