Cyclin-dependent kinase 8/β-catenin signalling contributes to tumourigenesis in prostate cancer and can be regulated by miR-216a-5p

Abstract

IntroductionCyclin-dependent kinase 8 (CDK8), as an oncogene, contributes to carcinogenesis in several cancer types. However, the role of CDK8 in prostate cancer (PCa) has not been completely clarified. The present study was to investigate the molecular mechanisms underlying the progression of PCa.Material and methodsIn human specimens, RT-qPCR and immunohistochemical (IHC) staining were used to detect the mRNA and protein expression of CDK8, respectively. In vitro experiments, MTT and colony formation assay, transwell assay, and Annexin V (FITC) double staining were performed to analyse cell proliferation, migration, invasion, and apoptosis, respectively.ResultsUp-regulation of CDK8 was observed in PCa tissues and associated with poor overall survival (OS) and disease-free survival (DFS). Knockdown of CDK8 by shRNA was able to repress cell proliferation and induce cell apoptosis in PC3 and DU145 cells, as well as reduce the protein expression of Wnt/-catenin pathway components. CDK8 was a direct target of miR-216a-5p, and overexpression of CDK8 reduced the antineoplastic activities of miR-216a-5p in vitro. Furthermore, miR-216a-5p could serve as an independent prognostic indicator for predicting the OS of PCa.ConclusionsmiR-216a-5p/CDK8/-catenin signalling cascade modulates the aggression of PCa. miR-216a-5p and CDK8, as promising therapeutic targets, might facilitate the development of therapeutic strategies for the treatment of PCa.