MicroRNA-192、ZEB1 对膀胱癌 上皮- 间质转化的影响

Effect of miR-192 and ZEB1 on epithelial-mesenchymal transition in bladder cancer

摘要:

目的 探讨microRNA-192（miR-192）和锌指结构转录因子1（ZEB1）在膀胱癌组织中的表 达及其意义。方法 选取96 例择期行手术治疗的膀胱癌患者作为膀胱癌组，同期留取外伤性膀胱破裂患者正 常膀胱黏膜组织41 例作为对照组，采用荧光定量聚合酶链反应检测不同组织中miR-192 和ZEB 1 基因的表达， Western blot 检测不同组织中ZEB1、E-cadherin 及Vimentin 蛋白的表达，分析其相关性。结果 膀胱癌组织 中miR-192表达水平低于对照组（P <0.05），而ZEB1 mRNA 表达水平高于对照组（P <0.05）。膀胱癌组织 中miR-192 和ZEB1 mRNA 表达水平与病理学分级、TNM 分期、淋巴结转移与否有关（P <0.05）。Western blot 检测结果显示，膀胱癌组织中ZEB1 和Vimentin 蛋白表达水平高于对照组（P <0.05），而E-cadherin 蛋 白表达水平低于对照组（P <0.05）。Pearson 相关性分析显示，膀胱癌组织中miR-192 与ZEB1、Vimentin 蛋 白表达水平呈负相关（r =-0.279 和-0.318，均P =0.000），与E-cadherin 蛋白表达水平呈正相关（r =0.376， P =0.000）。结论 miR-192 在膀胱癌组织中呈低表达，miR-192 可能通过负性调控ZEB1 促进上皮- 间质 转化过程，从而加速膀胱癌的浸润和转移。

Abstract:

Objective To investigate the expressions of microRNA-192 and zinc finger transcription factor 1 (ZEB1) in bladder cancer tissues and their effect on epithelial-mesenchymal transition (EMT). Methods Ninetysix cases of patients with bladder cancer undergoing elective surgery were selected. In the same period, 41 specimens of normal bladder mucosa of traumatic bladder rupture patients were selected as the control group. The expression levels of miR-192 and ZEB1 gene in different tissues were detected using qRT-PCR. The expression levels of ZEB1, E-cadherin and Vimentin proteins were tested by Western blot. The correlations among variables were analyzed by Pearson correlation analysis. Results The relative expression level of miR-192 in bladder cancer tissues was lower than that of the control group , while the relative expression level of ZEB1 mRNA was higher than that of the control group, the differences were statistically significant (P < 0.05). The relative expression levels of miR-192 and ZEB1 mRNA in the bladder cancer tissues were related with pathological grade, TNM stage and lymph node metastasis (P < 0.05). Western blot results showed that the relative expression levels of ZEB1 and Vimentin proteins in the bladder cancer tissues were higher than those in the control group, while the expression level of E-cadherin protein was lower than that of the control group, the differences were statistically significant (P < 0.05). Pearson correlation analysis showed that the relative expression level of miR-192 in the bladder cancer tissues was negatively correlated with the relative expression levels of ZEB1 and Vimentin proteins (r = -0.279 and -0.318, P < 0.05), while positively correlated with the relative expression level of E-cadherin protein (r = 0.376, P < 0.05). Conclusions The expression of miR-192 is low in bladder cancer tissues. miR-192 might promote EMT process through negative regulation of ZEB1, thereby accelerate bladder cancer invasion and metastasis.