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miR-145通过靶向ADAMTS5/ Wnt信号轴介导膀胱尿路上皮癌的肿瘤抑制作用。

miR-145-Mediated Tumor Suppression in Bladder Urothelial Carcinoma via Targeting the ADAMTS5/Wnt Signaling Axis.

作者信息

Wei Jiang, Feng Zhang L, Mao Cheny Y, Xi Huang, Ming Fu, Jun Chen

机构信息

Urology, Ezhou Central Hospital, Ezhou, CHN.

出版信息

Cureus. 2025 Aug 11;17(8):e89796. doi: 10.7759/cureus.89796. eCollection 2025 Aug.

DOI:10.7759/cureus.89796
PMID:40937200
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12421941/
Abstract

BACKGROUND

Bladder urothelial carcinoma (BLCA) is the most common urological tumor with high mortality. The present study aimed to investigate the role of miR-145 in the tumorigenesis of BLCA.

MATERIALS AND METHODS

The levels of miR-145 and ADAMTS5 were examined in BLCA specimens. BLCA cell lines T24 and 5637 were adopted for in vitro experiments. ADAMTS5 was verified as a downstream target of miR-145 using a luciferase reporter assay. Cell viability and apoptosis were detected using the CCK-8 assay and flow cytometry. Cell migratory and invasive capacities were examined by the transwell assay. The protein levels of ADAMTS5, E-cadherin, N-cadherin, and vimentin were analyzed by western blotting.

RESULTS

miR-145 was found to be negatively correlated to the expression of ADAMTS5 in BLCA specimens. ADAMTS5 was identified as a direct target of miR-145. In addition, PCR and western blotting showed that miR-145 overexpression reduced ADAMTS5 levels, suppressed cell viability, and induced cell apoptosis, whereas miR-145 knockdown triggered the opposite result. miR-145 has also been verified to impede epithelial-mesenchymal transition (EMT) activation in tumor progression.

CONCLUSION

The present study revealed that miR-145 negatively regulates the expression of ADAMTS5. This regulatory effect of miR-145 may be associated with the Wnt/β‑catenin signaling pathway. Therefore, miR-145 has the potential to be used as a biomarker for predicting the progression of BLCA.

摘要

背景

膀胱尿路上皮癌(BLCA)是最常见的泌尿系统肿瘤,死亡率高。本研究旨在探讨miR-145在BLCA肿瘤发生中的作用。

材料与方法

检测BLCA标本中miR-145和ADAMTS5的水平。采用BLCA细胞系T24和5637进行体外实验。使用荧光素酶报告基因检测法验证ADAMTS5是miR-145的下游靶点。采用CCK-8法和流式细胞术检测细胞活力和凋亡。通过Transwell实验检测细胞迁移和侵袭能力。采用蛋白质印迹法分析ADAMTS5、E-钙黏蛋白、N-钙黏蛋白和波形蛋白的蛋白水平。

结果

发现miR-145与BLCA标本中ADAMTS5的表达呈负相关。ADAMTS5被确定为miR-145的直接靶点。此外,PCR和蛋白质印迹显示,miR-145过表达降低了ADAMTS5水平,抑制了细胞活力,并诱导了细胞凋亡,而miR-145敲低则引发了相反的结果。miR-145也被证实可在肿瘤进展中阻碍上皮-间质转化(EMT)激活。

结论

本研究表明miR-145负向调节ADAMTS5的表达。miR-145的这种调节作用可能与Wnt/β-连环蛋白信号通路有关。因此,miR-145有潜力作为预测BLCA进展的生物标志物。

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