# Abnormal expression of miR-330-3p predicts post-prostatectomy urinary incontinence and regulates the function of urethral fibroblasts by targeting MMP2

## TL;DR

Low levels of miR-330-3p are linked to urinary incontinence after prostate surgery and may help predict and manage this condition.

## Contribution

This study identifies miR-330-3p as a potential biomarker for post-prostatectomy urinary incontinence and reveals its regulatory role via MMP2 in urethral fibroblasts.

## Key findings

- miR-330-3p is significantly downregulated in patients with post-prostatectomy urinary incontinence.
- miR-330-3p overexpression reduces inflammation and extracellular matrix degradation in urethral fibroblasts.
- MMP2 counteracts the effects of miR-330-3p on fibroblast function.

## Abstract

Post-prostatectomy urinary incontinence (PPUI) is a common complication for patients with prostate cancer after surgery. MicroRNA-330-3p (miR-330-3p) is down-regulated in stress urinary incontinence patients. However, its clinical role and regulatory mechanism in PPUI remain unknown.

To assess the clinical significance of miR-330-3p in PPUI and to explore the potential mechanisms via matrix metalloproteinase 2 (MMP2) regulation.

This study enrolled 135 ageing prostate cancer patients (86 without PPUI, 49 with PPUI). Reverse transcription PCR (RT-qPCR) was utilized to measure the levels of miR-330-3p, while Receiver operating characteristic (ROC) analysis was conducted to evaluate the predictive significance of miR-330-3p for PPUI. The proliferative of human urethral fibroblasts (HUFs) was assessed by Cell Counting Kit-8 (CCK-8) assay, while inflammatory cytokines were quantified via enzyme-linked immunosorbent assay (ELISA) kits. Western blot assay was employed to examine the protein levels of extracellular matrix (ECM) remodeling-related markers. The miR-330-3p/MMP2 interaction was validated by dual-luciferase assay.

miR-330-3p was significantly downregulated in PPUI patients, with low expression predicting PPUI. In HUFs, miR-330-3p overexpression inhibited IL-1β-induced hyperproliferation, inflammation, and ECM degradation. Overexpression of MMP2 counteracted the influence of miR-330-3p mimic on HUFs.

miR-330-3p is a potential biomarker for PPUI and regulates the function of urethral fibroblasts by targeting MMP2.