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微小RNA-132通过TGFβ1/Smad2信号通路抑制人膀胱癌的迁移、侵袭和上皮-间质转化。

MicroRNA-132 inhibits migration, invasion and epithelial-mesenchymal transition via TGFβ1/Smad2 signaling pathway in human bladder cancer.

作者信息

Wei Xi Chao, Lv Zhong Hua

机构信息

Department of Urology, Jining Hospital of Traditional Chinese Medicine, Jining 272000, Shandong, People's Republic of China.

Department of Urology, Jining No. 1 People's Hospital, Jining 272011, Shandong, People's Republic of China.

出版信息

Onco Targets Ther. 2019 Jul 23;12:5937-5945. doi: 10.2147/OTT.S201731. eCollection 2019.

Abstract

Increasing evidence shows that microRNAs play an important regulatory role in the development of several types of cancers. However, the role of microRNA-132 (miR-132) in human bladder cancer (BC) metastasis remains unclear. In this research, we aimed to investigate the effect of miR-132 on the cell migration and relate potential mechanism in BC. miR-132 expression level was assessed by quantitative real-time PCR (qRT-PCR) in 32 BC tissues and BC cell lines (T24). The function of miR-132 was evaluated by Transwell assay. Gene expression was determined by using qRT-PCR or Western blot. The results showed that miR-132 had a lower expression in BC tissues than in adjacent normal tissues. At the same time, compared to human normal urethral epithelium cells, the expression level of miR-132 was downregulated in T24 cell lines. miR-132 overexpression significantly inhibited migration and invasion capacities in T24 cells, while downregulation of miR-132 expression strengthened such capacities. Compared with those transfected with miR-132 mimic, EMT-related markers and TGFβ1/Smad2 expression levels were higher in T24 cells transfected with miR-132 inhibitor. Moreover, EMT-related markers and Smad2 expression levels was obviously increased in BC tissues compared to the adjacent normal tissues. The correlation result indicated that the expression of miR-132 and Smad2 was reversed. In short, our results suggest that miR-132 may play a suppressive role in the metastasis of BC cells via TGFβ1/Smad2 signaling pathway.

摘要

越来越多的证据表明,微小RNA在多种癌症的发展中发挥着重要的调节作用。然而,微小RNA - 132(miR - 132)在人类膀胱癌(BC)转移中的作用仍不清楚。在本研究中,我们旨在探讨miR - 132对BC细胞迁移的影响及其潜在机制。通过定量实时PCR(qRT - PCR)评估了32例BC组织和BC细胞系(T24)中miR - 132的表达水平。通过Transwell实验评估miR - 132的功能。使用qRT - PCR或蛋白质免疫印迹法测定基因表达。结果显示,miR - 132在BC组织中的表达低于相邻正常组织。同时,与人类正常尿道上皮细胞相比,miR - 132在T24细胞系中的表达水平下调。miR - 132过表达显著抑制T24细胞的迁移和侵袭能力,而miR - 132表达下调则增强了这些能力。与转染miR - 132模拟物的细胞相比,转染miR - 132抑制剂的T24细胞中EMT相关标志物和TGFβ1/Smad2表达水平更高。此外,与相邻正常组织相比,BC组织中EMT相关标志物和Smad2表达水平明显升高。相关性结果表明,miR - 132和Smad2的表达呈负相关。简而言之,我们的结果表明,miR - 132可能通过TGFβ1/Smad2信号通路在BC细胞转移中发挥抑制作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/10b0/6662166/325003f6cf2b/OTT-12-5937-g0001.jpg

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