Significantly altered expression of miR-511-3p and its target AKT3 has negative prognostic value in human prostate cancer.

PURPOSE

In this study, we assessed the expression and functions of microRNA-511-3p (miR-511-3p) in human prostate cancer (CaP).

METHODS

Gene expressions of miR-511-3p in CaP cells and human CaP tumors were assessed by qPCR. In VCaP and PC3 cells, miR-511-3p was overexpressed by lentivirus. The functions of miR-511-3p upregulation in regulating in vitro cancer proliferation, migration and in vivo cancer growth were assessed by MTT, transwell and transplantation assays, respectively. Downstream target gene of miR-511-3p, AKT3, was verified by dual-luciferase activity and qPCR assays. AKT3 was then overexpressed in miR-511-3p-upregulated CaP cells to assess its functions in miR-511-3p-mediated cancer regulation.

RESULTS

MiR-511-3p is significantly downregulated in CaP cell lines, and human CaP tumors. MiR-511-3p was further downregulated in T3/T4-staged CaP tumors and closely correlated with shorter overall survival among CaP patients. In VCaP and PC3 cells, lentiviral-induced miR-511-3p upregulation was acting as a tumor suppressor by inhibiting in vitro cancer proliferation, migration and in vivo transplantation. Human AKT3 gene was confirmed to be the downstream target of miR-511-3p in CaP. In miR-511-3p-upregulated VCaP and PC3 cells, forced-overexpression of AKT3 reversed the tumor suppressive effects of miR-511-3p in CaP.

CONCLUSION

MiR-511-3p may serve as a prognostic factor and tumor suppressor in CaP, very likely through inverse regulation of its downstream target gene of AKT3.