Background: Dysregulation 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.
Methods: Quantitative 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.
Results: There 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).
Conclusions: Excessive 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.
Keywords: biochemical recurrence; cell proliferation; miR-196a; p27kip1; prostate cancer.
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