miR-146b-5p promotes prostate cancer progression by targeting and negatively regulating FOXO3 and its mechanism

To investigate the expression and potential mechanism of action of miR-146b-5p in prostate cancer (PCa).

Quantification of miR-146b-5p and FOXO3 expression by RT-qPCR was performed on 140 paired PCa and normal adjacent tissues. Kaplan-Meier curves and Cox regression models were used to analyze the relationship between miR-146b-5p expression and 5-year survival outcomes. In vitro experiments were performed in PC-3 and 22RV1 cells to explore the regulatory relationship between miR-146b-5p and FOXO3.

miR-146b-5p is markedly upregulated in PCa tissues and cell lines, exhibiting a significant correlation with tumor stage, Gleason score, lymph node metastasis, and unfavorable prognosis. miR-146b-5p overexpression promoted PCa cell proliferation, migration, and invasion, while inhibition exerted opposite effects. Bioinformatics prediction and dual-luciferase assay confirmed that miR-146b-5p directly targeted the 3'UTR of FOXO3, negatively regulating its expression. Rescue experiments demonstrated that silencing FOXO3 reversed the inhibitory effects of miR-146b-5p inhibitor on PCa cell malignancy.

miR-146b-5p drives PCa progression through the targeted downregulation of FOXO3, implicating it as a promising prognostic marker and therapeutic target.