The Changes of MicroRNA Expression in the Corpus Cavernosum of a Rat Model With Cavernous Nerve Injury.

BACKGROUND: MicroRNAs (miRs) were found to be dysregulated in erectile dysfunction (ED) related to aging, type 2 diabetes mellitus, and vasculogenic abnormalities. However, miR expression in ED after radical prostatectomy (RP) is not known.

AIM: To detect abnormal miR expression in post-RP ED and analyze target genes and pathways.

METHODS: 16 Sprague Dawley rats were divided into bilateral cavernous nerve crush (BCNC) and control groups. 4 weeks after surgery, erectile function and histological change in the corpus cavernosum were evaluated. Total RNA from 3 rats from each group was isolated and processed to analyze the miR expression profiling by RNA sequencing. The top 10 up-regulated miR profiles were chosen directly and further validated in another 5 rats per each group by quantitative real-time polymerase chain (PCR) reaction. The target genes were predicted by online databases, including: TargetScan, mirwalk, miRanda, miRDB, and DIANA. The enrichment analysis of gene ontology-term analysis and Kyoto Encyclopedia of Genes and Genomes were performed by DAVID database.

OUTCOMES: Intra-cavernosal pressure, mean arterial pressure, smooth muscle content, and miR expression were measured.

RESULTS: Compared to the control group, the BCNC group had decreased intra-cavernosal/mean arterial pressure ratio and smooth muscle marker (α-smooth muscle actin). The sequence results showed that 124 miR expression dysregulated in the BCNC group, in which 122 miR expression were up-regulated. Of the 122 miRs, 21 miR expressions were increased above 2-fold. Among the top 10 up-regulated miRs, 4 miRs (miR-101a, miR-138, miR-338, and miR-142) levels were finally validated for over-expression by quantitative (PCR) reaction. The gene ontology analysis results showed that these 4 miRs could regulate the processes of cell apoptosis, fibrosis, endothelium, and smooth muscle cells function. The Kyoto Encyclopedia of Genes and Genomes pathway analysis showed the target genes were involved in 7 pathways related to ED.

CLINICAL TRANSLATION: Our findings provide novel insights into post-RP ED that may stimulate further studies to develop miR targeted therapy or damage detection for ED.

STRENGTHS & LIMITATIONS: To our knowledge, this is the first study to identify the miR profiling and function in the BCNC rat model. The rat model might not represent the human condition and the miR was only detected at 1 period. Besides that, there is a high probability of false positives for RNA sequence results.

CONCLUSION: 4 dysregulated miRs were found in the BCNC rat model, which may be related to post-RP ED by regulating apoptosis, fibrosis, endothelial, and smooth muscle cells. Liu C, Cao Y, Ko TC, et al. The Changes of MicroRNA Expression in the Corpus Cavernosum of a Rat Model With Cavernous Nerve Injury. J Sex Med 2018;15:958-965.