MicroRNA-204-5p Regulates Epithelial-to-Mesenchymal Transition during Human Posterior Capsule Opacification by Targeting SMAD4
MicroRNA-204-5p Regulates Epithelial-to-Mesenchymal Transition during Human Posterior Capsule Opacification by Targeting SMAD4
复制标题
MicroRNA-204-5p 通过靶向 SMAD4 调节人后囊混浊过程中上皮到间质的转变
DOI：
10.1167/iovs.12-10904
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发表时间：
2013-01-01
影响因子：
4.4
通讯作者：
Huang, Yusen
中科院分区：
文献类型：
--
作者：
Wang, Ye;Li, Wenfeng;Huang, Yusen
目的。探讨微小RNA（miRNA）在调节人后囊混浊（PCO）过程中上皮间质转化（EMT）中的作用。方法。使用 miRCURY LNA microRNA 阵列评估人类 PCO 组织和正常附着晶状体上皮细胞 (LEC) 的 miRNA 谱。使用体外人类供体囊袋模型研究 miRNA 在 PCO 期间 EMT 中的作用。通过Western blot和定量RT-PCR检测SMAD4、磷酸化SMAD2/3和一组EMT标志物的表达。结果。人类 PCO 组织和正常附着的 LEC 中的 miRNA 分析结果表明，在其他 miRNA 中，miR-204-5p 表达下调。利用生物信息学，我们确定 SMAD4（TGF-β/SMAD 信号传导的介质之一）作为 miR-204-5p 的预测靶标。原代LEC中miR-204-5p的过度表达增加了E-钙粘蛋白的表达并减少了波形蛋白和α平滑肌肌动蛋白的表达。此外，在 SMAD4 小干扰 RNA 存在的情况下，miR-204-5p 过表达增强了对 TGF-β 2 诱导的 EMT 的抑制。结论。我们的数据提供了确凿的证据，证明 miR-204-5p 通过靶向 SMAD4 进而靶向 TGF-β 信号传导，在直接调节 EMT 中发挥作用。由于其抑制 EMT 的能力，miR-204-5p 可能成为 PCO 治疗干预的新靶点。 （投资眼科可见科学。2013 年；54：323-332）DOI：10.1167/iovs.12-10904
PURPOSE. To investigate the role of microRNA (miRNA) in regulating epithelial-to-mesenchymal transition (EMT) during human posterior capsule opacification (PCO).METHODS. A miRCURY LNA microRNA array was used to evaluate the miRNA profiles of human PCO tissues and normal attached lens epithelial cells (LECs). An in vitro human donor capsular bag model was used to investigate the role of miRNAs in the EMT during PCO. The expression of SMAD4, phospho-SMAD2/3, and a panel of EMT markers was detected by Western blot and quantitative RT-PCR.RESULTS. The results of miRNA profiling in human PCO tissues and normal attached LECs demonstrated that, among other miRNAs, miR-204-5p expression was down-regulated. Using bioinformatics, we identified SMAD4, one of the mediators of TGF-beta/SMAD signaling, as a predicted target of miR-204-5p. Overexpression of miR-204-5p in primary LECs increased E-cadherin expression and decreased the expression of vimentin and alpha smooth muscle actin. Furthermore, miR-204-5p overexpression enhanced the repression of TGF-beta 2-induced EMT in the presence of SMAD4 small interfering RNA.CONCLUSIONS. Our data provide firm evidence of a role for miR-204-5p in the direct regulation of EMT through its targeting of SMAD4 and, consequently, TGF-beta signaling. Because of its ability to repress the EMT, miR-204-5p may be a novel target for PCO therapeutic intervention. (Invest Ophthalmol Vis Sci. 2013; 54: 323-332) DOI: 10.1167/iovs.12-10904