Upregulation of miR-1199-5p is associated with reduced type 2 5-α reductase in benign prostatic hyperplasia

Abstract

Background The 5-α reductase inhibitors (5-ARIs) are the first-line drug managing benign prostatic hyperplasia (BPH). Unfortunately, some patients showed no responses to 5-ARIs therapy, even suffering from worse symptoms. Although the decreased expression of 5-α reductase type 2(SRD5A2) in BPH tissues might explain the 5-ARIs therapy failure, the mechanisms underlying SRD5A2 decreased remained unelucidated. Objectives To investigate the mechanisms of microRNA regulating the variable expression of SRD5A2 resulting in treatment failure of 5-ARIs. Materials and methods The expression of SRD5A2 and microRNAs in BPH tissues and prostate cells were detected by immunohistochemistry, western blotting, and quantitative real-time PCR (qRT-PCR). Dual-luciferase reporter assay was performed to confirm that microRNA directly combine to SRD5A2 mRNA. The apoptosis of prostatic cells was detected by flow cytometry. Results 13.6%, 28.8%, and 57.6% of BPH tissues showed negative, weak, and strong positive SRD5A2 expression, respectively. Normal human prostatic epithelial cell line RWPE-1 strongly expressed SRD5A2, whereas the immortalized human prostatic epithelial cell line BPH-1 weakly expressed SRD5A2. miR-1199-5p expression level in BPH-1 was remarkably higher than that in RWPE-1(P༜0.001), and miR-1199-5p expression was significantly upregulated in BPH tissues with negative SRD5A2 expression than those with positive SRD5A2 expression. After miR-1199-5p mimics transfection, SRD5A2 expression was decreased markedly in RWPE-1 cells, whereas after miR-1199-5p inhibitor transfection, SRD5A2 expression increased in BPH-1 cells. Dual-luciferase reporter assay showed that miR-1199-5p could bind the 3’ untranslated region of SRD5A2. Additionally, miR-1199-5p could decrease the sensibility of finasteride (100 µM) on RWPE-1 cells. Conclusion Our results demonstrate that SRD5A2 expression varied in BPH tissues and miR-1199-5p might be one of the several factors contributing to differential SRD5A2 expression in BPH patients.