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Effects of microRNA-135a on the epithelial–mesenchymal transition migration and invasion of bladder cancer cells by targeting GSK3β through the Wnt/β-catenin signaling pathway

机译:通过Wnt /β-catenin信号通路靶向GSK3βmicroRNA-135a对膀胱癌细胞上皮-间质转化迁移和侵袭的影响

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摘要

This study investigated the effects of microRNA-135a (miR-135a) targeting of glycogen synthase kinase 3β (GSK3β) on the epithelial–mesenchymal transition (EMT), migration and invasion of bladder cancer (BC) cells by mediating the Wnt/β-catenin signaling pathway. BC and adjacent normal tissues were collected from 165 BC patients. Western blotting and quantitative real-time PCR were used to detect the expression of GSK3β, β-catenin, cyclinD1, E-cadherin, vimentin and miR-135a in BC tissues and cells. Cells were assigned to blank, negative control (NC), miR-135a mimics, miR-135a inhibitors, small interfering RNA (siRNA)-GSK3β or miR-135a inhibitors+siRNA-GSK3β groups. miR-135a, β-catenin, cyclinD1 and vimentin expression increased, while GSK3β and E-cadherin expression decreased in BC tissues compared with adjacent normal tissues. Compared with the blank and NC groups, the expression of miR-135a, β-catenin, cyclinD1 and vimentin was higher, and cell proliferation, migration, invasion and tumor growth were increased in the miR-135a mimics and siRNA-GSK3β groups. These groups showed an opposite trend in GSK3β and E-cadherin expression and cell apoptosis. The miR-135a inhibitors group was inversely correlated with the blank and NC groups. It was concluded that miR-135a accelerates the EMT, invasion and migration of BC cells by activating the Wnt/β-catenin signaling pathway through the downregulation of GSK3β expression.
机译:这项研究通过介导Wnt /β-连环蛋白信号通路。从165名BC患者中收集了BC和邻近的正常组织。 Western blotting和实时荧光定量PCR检测GSK3β,β-catenin,cyclinD1,E-cadherin,波形蛋白和miR-135a在BC组织和细胞中的表达。将细胞分配给空白,阴性对照(NC),miR-135a模拟物,miR-135a抑制剂,小干扰RNA(siRNA)-GSK3β或miR-135a抑制剂+siRNA-GSK3β组。与邻近的正常组织相比,BC组织中的miR-135a,β-catenin,cyclinD1和波形蛋白表达增加,而GSK3β和E-cadherin表达下降。与空白组和NC组相比,miR-135a模拟组和siRNA-GSK3β组的miR-135a,β-catenin,cyclinD1和波形蛋白的表达更高,并且细胞增殖,迁移,侵袭和肿瘤生长增加。这些组在GSK3β和E-钙粘着蛋白表达以及细胞凋亡中显示出相反的趋势。 miR-135a抑制剂组与空白组和NC组呈负相关。结论是,miR-135a通过下调GSK3β表达激活Wnt /β-catenin信号通路,从而加速BC细胞的EMT,侵袭和迁移。

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