Jiang Shi-Bin, He Xu-Jun, Xia Ying-Jie, Hu Wei-Jian, Luo Jun-Gang, Zhang Jun, Tao Hou-Quan
Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China; Wenzhou Medical University, Wenzhou, People's Republic of China.
Department of Surgery, Zhejiang Provincial People's Hospital, Hangzhou, People's Republic of China; Key Laboratory of Gastroenterology of Zhejiang Province, Zhejiang Provincial People's Hospital, Hangzhou, Zhejiang, People's Republic of China.
Onco Targets Ther. 2016 Apr 18;9:2305-15. doi: 10.2147/OTT.S101853. eCollection 2016.
MicroRNA (miR)-145-5p has been reported to function as a suppressor of cancer and plays an important role in cancer invasiveness. Epithelial-mesenchymal transition (EMT) is an important process in cancer invasion and migration. However, the involvement of miR-145-5p in EMT in human gastric cancer (GC) remains unclear. In this study, we aimed to investigate the molecular mechanisms by which miR-145-5p regulates EMT in GC invasiveness. We used quantitative real-time polymerase chain reaction to investigate the miR-145-5p expression level in GC and matched normal tissues. The effects of miR-145-5p on GC cell invasion and migration abilities were evaluated using Transwell models. The relationships among miR-145-5p and zinc-finger E-box binding homeobox 2 (ZEB2), E-cadherin, and N-cadherin were analyzed by quantitative real-time polymerase chain reaction and Western blot analyses. miR-145-5p levels in primary GC tissues obtained from 60 patients were significantly downregulated, compared to those in paired normal tissues. Lauren classification, depth of tumor invasion, lymph node metastasis, lymphatic invasion, and tumor-node-metastasis stage were associated with miR-145-5p expression. miR-145-5p inhibits the expression of the candidate target gene ZEB2 to delay the invasion and migration of GC cells. ZEB2 acts as transcriptional repressor of E-cadherin, while miR-145-5p is known to suppress N-cadherin directly to regulate EMT. Therefore, we concluded that miR-145-5p may target N-cadherin and ZEB2 directly to influence EMT.
据报道,微小RNA(miR)-145-5p发挥癌症抑制因子的作用,在癌症侵袭过程中起重要作用。上皮-间质转化(EMT)是癌症侵袭和迁移中的一个重要过程。然而,miR-145-5p在人胃癌(GC)的EMT过程中的作用仍不清楚。在本研究中,我们旨在探究miR-145-5p调控GC侵袭过程中EMT的分子机制。我们采用定量实时聚合酶链反应来研究GC组织及配对正常组织中miR-145-5p的表达水平。使用Transwell模型评估miR-145-5p对GC细胞侵袭和迁移能力的影响。通过定量实时聚合酶链反应和蛋白质免疫印迹分析来分析miR-145-5p与锌指E盒结合同源框2(ZEB2)、E-钙黏蛋白和N-钙黏蛋白之间的关系。与配对的正常组织相比,从60例患者获取的原发性GC组织中miR-145-5p水平显著下调。Lauren分类、肿瘤浸润深度、淋巴结转移、淋巴管浸润和肿瘤-淋巴结-转移分期与miR-145-5p表达相关。miR-145-5p抑制候选靶基因ZEB2的表达,以延缓GC细胞的侵袭和迁移。ZEB2作为E-钙黏蛋白的转录抑制因子,而miR-145-5p已知可直接抑制N-钙黏蛋白以调节EMT。因此,我们得出结论,miR-145-5p可能直接靶向N-钙黏蛋白和ZEB2以影响EMT。