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微小RNA-150在骨肉瘤中表达下调,并通过靶向Rho相关卷曲螺旋蛋白激酶1抑制细胞增殖、迁移和侵袭。

miR-150 is downregulated in osteosarcoma and suppresses cell proliferation, migration and invasion by targeting ROCK1.

作者信息

Li Chang-Hui, Yu Teng-Bo, Qiu Hong-Wei, Zhao Xia, Zhou Chuan-Li, Qi Chao

机构信息

Department of Orthopedics, Affiliated Hospital of Qingdao University, Qingdao, Shandong 266003, P.R. China.

Department of Orthopedics, People's Hospital of Rizhao, Rizhao, Shandong 276826, P.R. China.

出版信息

Oncol Lett. 2017 Apr;13(4):2191-2197. doi: 10.3892/ol.2017.5709. Epub 2017 Feb 9.

Abstract

Osteosarcoma (OS) is the most common form of bone malignancy in children and adolescents. A class of molecules known as microRNAs (miRNAs) have been routinely associated in the development and progression of OS. The present study was centered on the less well-known miRNA, miRNA (miR)-150, and its role in OS was investigated. The levels of miR-150 were examined in 40 tissue specimens from patients with OS and adjacent normal tissues using reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis. In addition the expression levels of miR-150 were examined in three OS cell lines and a normal osteoblast cell line. Cell proliferation, migration and invasion assays were performed to establish the correlation between miR-150 and metastasis. The potential targets of miR-150 were theoretically predicted and one high-scoring target, Rho-associated kinase 1 (ROCK1), was established to be a direct target using RT-qPCR and western blot analyses and Pearson's correlation analysis. The results indicated that miR-150 was downregulated in tissues from patients with OS and cell lines. Secondly, it was shown that the overexpression of miR-150 was inversely correlated with OS cell proliferation, migration and invasion. It was also shown that miR-150 negatively regulated the gene expression of ROCK1 in the OS cell lines. Finally, the interaction between miR-150 and ROCK1 was established and it was shown that miR-150 directly targeted ROCK1. In conclusion, miR-150 was found to be a tumor suppressor, and the suppression of miR-150 resulted in elevation in the levels of ROCK1. This interaction between miR-150 and ROCK1 may be key in the progression of OS. Furthermore, miR-150 or ROCK1 may be potential therapeutic targets for the treatment of OS.

摘要

骨肉瘤(OS)是儿童和青少年中最常见的骨恶性肿瘤形式。一类被称为微小RNA(miRNA)的分子经常与骨肉瘤的发生和发展相关。本研究聚焦于鲜为人知的miRNA,即miR-150,并对其在骨肉瘤中的作用进行了研究。使用逆转录-定量聚合酶链反应(RT-qPCR)分析检测了40例骨肉瘤患者组织标本及相邻正常组织中miR-150的水平。此外,还检测了三种骨肉瘤细胞系和一种正常成骨细胞系中miR-150的表达水平。进行细胞增殖、迁移和侵袭实验以确定miR-150与转移之间的相关性。从理论上预测了miR-150的潜在靶标,并通过RT-qPCR、蛋白质印迹分析和Pearson相关性分析确定了一个高分靶标,即Rho相关激酶1(ROCK1)为直接靶标。结果表明,miR-150在骨肉瘤患者的组织和细胞系中表达下调。其次,研究表明miR-150的过表达与骨肉瘤细胞的增殖、迁移和侵袭呈负相关。还表明miR-150在骨肉瘤细胞系中负调控ROCK1的基因表达。最后,确定了miR-150与ROCK1之间的相互作用,表明miR-150直接靶向ROCK1。总之,发现miR-

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b346/5403695/61ed36b8c687/ol-13-04-2191-g00.jpg

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