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微小RNA-145通过靶向人胶质母细胞瘤中的解聚素金属蛋白酶19抑制上皮-间质转化。

MiR-145 inhibits the epithelial-to-mesenchymal transition via targeting ADAM19 in human glioblastoma.

作者信息

Wang Xingqiang, Wang Enqin, Cao Jun, Xiong Feng, Yang Yonglin, Liu Haitao

机构信息

Department of Neurosurgery, Rizhao People's Hospital, Jining Medical University, Rizhao 276826, Shandong, China.

Clinical Skill Training Center, Rizhao People's Hospital, Jining Medical University, Rizhao 276826, Shandong, China.

出版信息

Oncotarget. 2017 Sep 30;8(54):92545-92554. doi: 10.18632/oncotarget.21442. eCollection 2017 Nov 3.

Abstract

In recent years, increasing studies demonstrated that miR-145 plays a tumor suppressor role in many human cancers. In the present study, we evaluated the expression of miR-145 and A Disintegrin and Metalloproteinase 19 (ADAM19) in glioblastoma multiforme (GBM) tissues and cells. Furthermore, we investigated the mechanisms underlying miR-145/ADAM19-induced GBM biology. Here, we found that miR-145 expression was down-regulated, while ADAM19 expression was up-regulated in GBM tissues and cells. Moreover, miR-145 mimics repressed U87 and U251 cell proliferation, migration and invasion. miR-145 mimics also inhibited the epithelial-to-mesenchymal transition (EMT) of U87 and U251 cells. Mechanically, the 3' untranslated region (3'-UTR) of ADAM19 mRNA was a direct target for miR-145. In addition, ADAM19 over-expression also partially abrogated miR-145-inhibited EMT. In conclusion, this work suggested that high miR-145 expression inhibited EMT of GBM cells by targeting ADAM19. Thus miR-145/ADAM19 can be suggested as a novel target for GBM patients.

摘要

近年来,越来越多的研究表明,miR-145在许多人类癌症中发挥肿瘤抑制作用。在本研究中,我们评估了多形性胶质母细胞瘤(GBM)组织和细胞中miR-145和去整合素金属蛋白酶19(ADAM19)的表达。此外,我们研究了miR-145/ADAM19诱导GBM生物学行为的潜在机制。在此,我们发现GBM组织和细胞中miR-145表达下调,而ADAM19表达上调。此外,miR-145模拟物可抑制U87和U251细胞的增殖、迁移和侵袭。miR-145模拟物还可抑制U87和U251细胞的上皮-间质转化(EMT)。机制上,ADAM19 mRNA的3'非翻译区(3'-UTR)是miR-145的直接靶点。此外,ADAM19的过表达也部分消除了miR-145抑制的EMT。总之,这项工作表明高表达的miR-145通过靶向ADAM19抑制GBM细胞的EMT。因此,miR-145/ADAM19可被认为是GBM患者的一个新靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2570/5696202/19d235f3c38c/oncotarget-08-92545-g001.jpg

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