Liu Tianming, Nie Fang, Yang Xianggui, Wang Xiaoyan, Yuan Yue, Lv Zhongshi, Zhou Li, Peng Rui, Ni Dongsheng, Gu Yuping, Zhou Qin, Weng Yaguang
Key Laboratory of Laboratory Medical Diagnostics Designated by Chinese Ministry of Education, College of Laboratory Medicine, Chongqing Medical University, Chongqing 400016, P.R. China.
Mol Med Rep. 2015 Nov;12(5):7403-11. doi: 10.3892/mmr.2015.4374. Epub 2015 Sep 25.
Over the last few decades, the epithelial-to-mesenchymal transition (EMT) has been identified as being involved in a number of aspects of physiological processes and various pathological events, including embryonic development and renal fibrosis. Transforming growth factor‑β receptor 2 (TGFβR2) is a widely studied gene, which fulfils a vital role in the TGFβ signaling pathway and exerts a crucial function in the progression of EMT. Previous studies demonstrated that the dysregulation of microRNAs (miRNAs) is considered to be associated with the EMT process. However, the precise functional involvement of miRNAs in EMT remains to be fully elucidated. In the present study, the level of miR‑590 was decreased in an EMT model in vitro and in vivo. Furthermore, the overexpression of miR‑590 inhibited EMT by upregulating the epithelial marker, E‑cadherin, and downregulating the mesenchymal markers, laminin, α‑smooth muscle actin (α‑SMA) and collagen, in the human kidney 2 (HK2) cell line. Furthermore, TGFβR2 was negatively regulated by miR‑590. In addition, performing a knockdown of TGFβR2 with small‑interfering RNA had an effect similar to miR‑590 on EMT in the HK2 cell line, whereas the transfection of pCMV‑tag2B‑TGFβR2 reversed the effect of miR‑590 on EMT in HK2 cells. Taken together, the present study demonstrated that miR-590 is a novel EMT-suppressive microRNA, which targets TGFβR2.
在过去几十年中，上皮-间质转化（EMT）已被确定参与生理过程的多个方面以及各种病理事件，包括胚胎发育和肾纤维化。转化生长因子-β受体2（TGFβR2）是一个被广泛研究的基因，它在TGFβ信号通路中发挥重要作用，并在EMT进程中发挥关键功能。先前的研究表明，微小RNA（miRNA）的失调被认为与EMT过程有关。然而，miRNA在EMT中的确切功能仍有待充分阐明。在本研究中，miR-590的水平在体外和体内的EMT模型中均降低。此外，miR-590的过表达通过上调上皮标志物E-钙黏蛋白，并下调人肾2（HK2）细胞系中的间质标志物层粘连蛋白、α-平滑肌肌动蛋白（α-SMA）和胶原蛋白来抑制EMT。此外，TGFβR2受到miR-590的负调控。另外，用小干扰RNA敲低TGFβR2对HK2细胞系中的EMT产生的作用与miR-590类似，而转染pCMV-tag2B-TGFβR2可逆转miR-590对HK2细胞中EMT的作用。综上所述，本研究表明miR-590是一种新型的抑制EMT的微小RNA，其靶标为TGFβR2。
