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

机译:miR-150在骨肉瘤中下调并通过靶向ROCK1抑制细胞增殖迁移和侵袭

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摘要

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.
机译:骨肉瘤(OS)是儿童和青少年中最常见的骨恶性肿瘤形式。一类称为微RNA(miRNA)的分子通常与OS的发展和进程相关。本研究集中在鲜为人知的miRNA miRNA(miR)-150,并研究了其在OS中的作用。使用逆转录定量聚合酶链反应(RT-qPCR)分析检查了来自OS患者和邻近正常组织的40个组织样本中的miR-150水平。另外,在三种OS细胞系和正常成骨细胞系中检查了miR-150的表达水平。进行细胞增殖,迁移和侵袭测定以建立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,并使用RT-qPCR和Western blot分析以及Pearson相关分析,将一个高得分靶标Rho相关激酶1(ROCK1)建立为直接靶标。结果表明,患有OS和细胞株的患者组织中的miR-150被下调。其次,表明miR-150的过表达与OS细胞的增殖,迁移和侵袭成反比。还显示了miR-150在OS细胞系中负调控ROCK1的基因表达。最后,建立了miR-150与ROCK1的相互作用,结果表明miR-150直接靶向ROCK1。总之,发现miR-150是一种肿瘤抑制因子,对miR-150的抑制导致ROCK1水平升高。 miR-150和ROCK1之间的这种相互作用可能是OS进展的关键。此外,miR-150或ROCK1可能是OS的潜在治疗靶标。

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