Benign prostatic hyperplasia (BPH) is an age-related disease in men. Lower urinary tract symptoms associated with BPH substantially impair daily functioning and quality of life. Prostate tissues from patients with BPH exhibit microenvironmental changes such as fibrosis, and an increased proportion of myofibroblast cells has also been observed. We evaluated the epithelial–mesenchymal transition (EMT) and myofibroblast proliferation in E2-induced BPH-1, RWPE-1, and WPMY-1 cells. Based on recent reports that miR-16-5p is downregulated in BPH patient tissues, we investigated the effect of miR-16-5p in E2-stimulated BPH-1, RWPE-1, and WPMY-1 cells using qRT-PCR, wound-healing assay, and Western blotting. We first examined the role of miR-16-5p in human prostate cell lines and human BPH tissues. In BPH patient prostate tissues, the levels of vimentin, cytokeratin17, and TGF-β, known as EMT and fibrosis-related proteins were increased. Our experiments further showed that E2 enhanced EMT in epithelial cells and promoted the proliferation of myofibroblasts. In E2-stimulated RWPE-1 and BPH-1 cells, E2 upregulated PCNA, CTGF, cytokeratin17, GPER, and HIF-1α. In WPMY-1 cells, E2 increased the expression of GPER, HIF-1α, phosphorylated-CREB, cyclin E, Cyclin D1, and PCNA. Notably, miR-16-5p inhibited E2-induced cell proliferation in WPMY-1 cells and suppressed E2-induced EMT in RWPE-1 and BPH-1 cells. Taken together, these results suggest that miR-16-5p warrants further investigation as a potential regulator that may help inhibit or alleviate BPH. Modulation of E2 signaling and miR-16-5p may represent a promising strategy for improving prostatic hyperplasia.
Kim et al. (Fri,) studied this question.