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微小RNA-202-5p通过靶向Rho相关卷曲螺旋蛋白激酶1抑制骨肉瘤细胞的迁移和侵袭。

miR-202-5p inhibits the migration and invasion of osteosarcoma cells by targeting ROCK1.

作者信息

Li Congda, Ma Deying, Yang Jinhu, Lin Xiangbo, Chen Bo

机构信息

Department of Orthopedic, People's Hospital of Rizhao, Rizhao, Shandong 276800, P.R. China.

出版信息

Oncol Lett. 2018 Jul;16(1):829-834. doi: 10.3892/ol.2018.8694. Epub 2018 May 10.

Abstract

Many studies have shown that microRNA regulates the development and treatment of osteosarcoma (OS). In many human cancer studies, the expression of microRNA-202 has been shown to be abnormal. The aim of the study was to examine the role of miR-202-5p in the occurrence and formation of OS. miR-202-5p and Rho-associated coiled-coil containing protein kinase 1 (ROCK1) levels were assessed using RT-qPCR in OS tissues and cell lines. The cell migrating and invasive abilities were detected by the Transwell assay in OS. Moreover, the relationship between miR-202-5p and ROCK1 was verified via luciferase reporter assay. The protein level of ROCK1 was identified by western blot analysis. Downregulation of miR-202-5p was identified in OS tissues and cell lines. In addition, the miR-202-5p overexpression had inhibitory action for cell migration and invasion in OS. Moreover, miR-202-5p directly targeted ROCK1 and negatively regulated its expression. Upregulation of ROCK1 had a carcinogenic effect in OS. Furthermore, the upregulation of ROCK1 restored the suppressive effect of miR-202-5p. miR-202-5p, in turn, weakened the abilities of cell migration and invasion in OS by inhibiting ROCK1 expression. As a result, miR-202-5p may be developed as a potential pathway in the reatment of OS.

摘要

许多研究表明,微小RNA可调节骨肉瘤(OS)的发展及治疗。在许多人类癌症研究中,已表明微小RNA-202的表达存在异常。本研究的目的是检测miR-202-5p在OS发生及形成过程中的作用。采用RT-qPCR检测OS组织及细胞系中miR-202-5p和含Rho相关卷曲螺旋蛋白激酶1(ROCK1)的水平。通过Transwell实验检测OS细胞的迁移和侵袭能力。此外,通过荧光素酶报告基因实验验证miR-202-5p与ROCK1之间的关系。通过蛋白质免疫印迹分析鉴定ROCK1的蛋白水平。在OS组织及细胞系中发现miR-202-5p表达下调。此外,miR-202-5p过表达对OS细胞的迁移和侵袭具有抑制作用。而且,miR-202-5p直接靶向ROCK1并对其表达起负向调节作用。ROCK1的上调在OS中具有致癌作用。此外,ROCK1的上调恢复了miR-202-5p的抑制作用。反过来,miR-202-5p通过抑制ROCK1表达减弱了OS细胞的迁移和侵袭能力。因此,miR-202-5p可能会被开发成为治疗OS的潜在途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c550/6019893/ffe2ee95221d/ol-16-01-0829-g00.jpg

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