Regulatory interplay of miR-361-5p/TWIST1/SOX4 axis modulating epithelial-mesenchymal transition cascades in metastatic prostate cancer.

Prostate cancer (PCa) progression and metastasis remain significant challenges in clinical oncology. miR-361-5p has been identified to function as an important tumor suppressor in multiple human malignancies. However, the clinical significance and biological role of miR-361-5p in PCa remain unclear. The present study was conducted to investigate the molecular mechanisms in metastatic PCa by using various experimental methods in vitro and in vivo. miR-361-5p was significantly downregulated in PCa cells and tissues. Overexpression of miR-361-5p inhibited proliferation, migration, and invasion in vitro, and suppressed tumor growth and lung metastasis in vivo. Mechanistically, miR-361-5p directly targeted TWIST1, reducing its protein levels and transcriptional activity; restoration of TWIST1 rescued the metastatic phenotype, confirming functional targeting. Importantly, miR-361-5p also regulated SOX4 via TWIST1 and formed a negative feedback loop with SOX4, reinforcing the suppression of metastasis. This TWIST1/SOX4 axis drove a reversal of epithelial-mesenchymal transition, marked by increased E-cadherin and decreased Vimentin and Fibronectin expression. The present study, for the first time, suggests that miR-361-5p functions as a tumor suppressor in PCa by modulating the TWIST1/SOX4 axis and EMT. These insights offer new therapeutic avenues for targeting miRNAs in metastatic PCa.