miR‐196a‐mediated downregulation of p27kip1 protein promotes prostate cancer proliferation and relates to biochemical recurrence after radical prostatectomy

Abstract

AbstractBackgroundDysregulation of microRNAs has performed vital gene regulatory functions in the genesis, progression, and prognosis of multiple malignant tumors. This study aimed to elucidate the regulatory mechanism of miR‐196a in prostate cancer (PCa) and explore its clinical significance.MethodsQuantitative real‐time polymerase chain reaction was implemented to examine miR‐196a and p27kip1 messenger RNA expression in PCa. Cell proliferation was evaluated via Cell Counting Kit‐8, colony formation, and nude mouse tumorigenicity assays. Luciferase reporter assay was applied to identify target genes. p27kip1 protein expression in PCa was investigated using Western blot analysis and immunohistochemistry.ResultsThere was a dramatic upregulation of miR‐196a in PCa. Upregulated miR‐196a was related to worse Gleason score (GS), later pathological stage, and poor biochemical recurrence (BCR)‐free survival. In vivo and in vitro experiments exhibited that miR‐196a promoted PCa proliferation and expedited G1/S‐phase progression through the downregulation of p27kip1 protein. Additionally, p27kip1 protein was distinctly downregulated in PCa. Low p27kip1 protein expression had a strong correlation with increased GS and was an independent predictor of BCR after radical prostatectomy (RP).ConclusionsExcessive expression of miR‐196a and subsequent downregulation of p27kip1 protein play essential roles in promoting PCa proliferation and leading to BCR after RP. miR‐196a and its target p27kip1 may become novel molecular biomarkers and therapeutic targets for PCa.