Abstract
Prostate cancer (PCa) is an androgen‑dependent disease. Androgen receptor (AR) has a crucial role in the development and progression of PCa. Recently, several microRNAs (miRNAs/miRs) involved in AR regulation have been associated with castration‑resistant prostate cancer (CRPC), the terminal stage of PCa. Nevertheless, the precise mechanism remains unclear. The present study aimed to identify a novel miR‑149 regulatory network and potential therapeutic target for CRPC. It was found that ectopic expression of miR‑149 mimic could inhibit AR expression, repress epithelial‑mesenchymal transition, induce cell cycle arrest and apoptosis in CRPC cell line C4‑2, whereas the miR‑149 inhibitor exerted the opposite effects. Furthermore, it was also revealed that miR‑149 could reduce the functional activity of the PI3K/Akt1 signaling pathway by targeting Akt1 protein, the key regulatory factor of the PI3K/Akt1 signaling pathway. Knockdown of Akt1 by short hairpin RNA increased apoptosis, reduced proliferation, and restrained migration and invasion in CRPC cells, with the effect of AR inhibition. In conclusion, these results revealed that miR‑149 acts as a tumor suppressor in CRPC cell line C4‑2 and restrains its progression through the AR signaling pathway by targeting Akt1. The miR‑149/Akt1/AR regulatory pathway may represent a novel PCa therapeutic target.