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miR-365 通过直接靶向骨肉瘤中的 CYR61 发挥肿瘤抑制作用。

miR-365 functions as a tumor suppressor by directly targeting CYR61 in osteosarcoma.

机构信息

College of Bioengineering, Jilin Agricultural Science and Technology University, Jilin City 132101, PR China.

College of Bioengineering, Jilin Agricultural Science and Technology University, Jilin City 132101, PR China.

出版信息

Biomed Pharmacother. 2018 Feb;98:531-537. doi: 10.1016/j.biopha.2017.12.086. Epub 2017 Dec 27.

DOI:10.1016/j.biopha.2017.12.086
PMID:29287201
Abstract

Increasing evidence indicates that microRNAs(miRNAs) are often aberrantly expressed in osteosarcoma (OS) and play critical roles in OS tumorigenesis. Therefore, the discovery of miRNAs may provide a new and powerful tool for understanding the mechanismof OS initiation and development. The aim of this study was to investigate the functional significance of miR-365 and identify its possible mechanism in OS cells. Here, wefound that the expression level of miR-365 is significantly downregulated in OS tissues and cell lines, and its expression isassociated with the clinical stage, distant metastasis, tumor grade, and poor overall survival rate. The overexpression of miR-365 is able to inhibit cell proliferation, migration, and invasion in Saos-2 and MG-63 cells. Moreover, the cysteine-rich angiogenic inducer 61 (CYR61) has been identified as a target of miR-365 in OS cells, and its expression is found to be significantly increased in OS tissues, which is negatively correlated with miR-365. Furthermore, CYR61 overexpression significantly attenuated the suppressive effects of miR-365 on the proliferation, migration, and invasion of Saos-2 and MG-63 cells. Therefore, we consider that miR-365 acts as a tumor suppressor in OS, partly, by targeting CYR61 expression.

摘要

越来越多的证据表明,微小 RNA(miRNA)在骨肉瘤(OS)中经常异常表达,并在 OS 肿瘤发生中发挥关键作用。因此,miRNA 的发现可能为理解 OS 起始和发展的机制提供新的有力工具。本研究旨在探讨 miR-365 的功能意义,并确定其在 OS 细胞中的可能机制。在这里,我们发现 miR-365 的表达水平在 OS 组织和细胞系中显著下调,其表达与临床分期、远处转移、肿瘤分级和总生存率差有关。miR-365 的过表达能够抑制 Saos-2 和 MG-63 细胞的增殖、迁移和侵袭。此外,富含半胱氨酸的血管生成诱导因子 61(CYR61)已被确定为 OS 细胞中 miR-365 的靶标,并且其在 OS 组织中的表达明显增加,与 miR-365 呈负相关。此外,CYR61 过表达显著减弱了 miR-365 对 Saos-2 和 MG-63 细胞增殖、迁移和侵袭的抑制作用。因此,我们认为 miR-365 通过靶向 CYR61 表达在 OS 中部分发挥肿瘤抑制作用。

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