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

IF 2.7 3区生物学

Hereditas Pub Date : 2025-06-18 DOI:10.1186/s41065-025-00475-8

Xiaoying Feng, Yuanyuan Mi, Mengye Weng

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引用次数: 0

Abstract

Background: 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.

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

Methods: 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.

Result: 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.

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

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miR-330-3p异常表达可预测前列腺切除术后尿失禁，并通过靶向MMP2调控尿道成纤维细胞功能。

背景：前列腺切除术后尿失禁（PPUI）是前列腺癌术后常见并发症。MicroRNA-330-3p （miR-330-3p）在应激性尿失禁患者中下调。然而，其在PPUI中的临床作用和调节机制尚不清楚。目的：评价miR-330-3p在PPUI中的临床意义，并通过基质金属蛋白酶2 （MMP2）调控探讨其潜在机制。方法：本研究纳入135例老年前列腺癌患者（无PPUI 86例，有PPUI 49例）。采用逆转录PCR （RT-qPCR）检测miR-330-3p水平，采用Receiver operating characteristic （ROC）分析评价miR-330-3p对PPUI的预测意义。采用细胞计数试剂盒-8 （CCK-8）检测人尿道成纤维细胞（HUFs）的增殖能力，采用酶联免疫吸附试验（ELISA）检测炎症因子。采用Western blot法检测细胞外基质（ECM）重塑相关标志物的蛋白水平。通过双荧光素酶测定验证miR-330-3p/MMP2相互作用。结果：miR-330-3p在PPUI患者中显著下调，低表达可预测PPUI。在HUFs中，miR-330-3p过表达抑制il -1β诱导的过度增殖、炎症和ECM降解。MMP2的过表达抵消了miR-330-3p mimic对HUFs的影响。结论：miR-330-3p是PPUI的潜在生物标志物，通过靶向MMP2调控尿道成纤维细胞的功能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.