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微小RNA-26a通过Wnt/β-连环蛋白信号通路诱导骨肉瘤细胞生长和转移。

MicroRNA-26a induces osteosarcoma cell growth and metastasis via the Wnt/β-catenin pathway.

作者信息

Qu Feng, Li Chun-Bao, Yuan Bang-Tuo, Qi Wei, Li Hong-Liang, Shen Xue-Zhen, Zhao Gang, Wang Jiang-Tao, Liu Yu-Jie

机构信息

Department of Orthopedics, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, P.R. China; Department of Orthopedics, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.

Department of Orthopedics, Chinese People's Liberation Army General Hospital, Beijing 100853, P.R. China.

出版信息

Oncol Lett. 2016 Feb;11(2):1592-1596. doi: 10.3892/ol.2015.4073. Epub 2015 Dec 31.

Abstract

MicroRNAs (miRNAs/miRs) are a type of highly conserved, small non-coding RNA that are vital to the post-transcriptional regulation of gene expression via base pairing with target mRNA 3'-untranslated regions (3'-UTRs). Several studies have indicated that the abnormal expression of miRNAs occurs frequently in human osteosarcoma (OS). In the present study, the role of miR-26a in the progression and metastasis of OS was investigated using reverse transcription-quantitative polymerase chain reaction, a luciferase activity assay, cell viability assay, migration and invasion assays, transfection and western blot analysis. miR-26a was upregulated in OS tissues and cell lines, and the expression of miR-26a was indicated to affect the proliferation, migration and invasion of OS Saos-2 cells. At the molecular level, the results showed that glycogen synthase kinase-3β (GSK-3β) was identified as a target of miR-26a, and the ectopic expression of miR-26a inhibited GSK-3β by directly binding to the 3'-UTR. Therefore, the expression of miR-26a was negatively correlated with GSK-3β in the OS tissues. These data suggest that miR-26a is significant in the proliferation of human OS cells due to the direct regulation of Wnt/β-catenin signaling.

摘要

微小RNA(miRNA/miR)是一类高度保守的小型非编码RNA,通过与靶mRNA的3'-非翻译区(3'-UTR)碱基配对,对基因表达的转录后调控至关重要。多项研究表明,miRNA的异常表达在人类骨肉瘤(OS)中频繁发生。在本研究中,采用逆转录定量聚合酶链反应、荧光素酶活性测定、细胞活力测定、迁移和侵袭测定、转染及蛋白质免疫印迹分析,研究了miR-26a在骨肉瘤进展和转移中的作用。miR-26a在骨肉瘤组织和细胞系中上调,且miR-26a的表达影响骨肉瘤Saos-2细胞的增殖、迁移和侵袭。在分子水平上,结果表明糖原合酶激酶-3β(GSK-3β)被确定为miR-26a的靶标,miR-26a的异位表达通过直接结合3'-UTR抑制GSK-3β。因此,在骨肉瘤组织中,miR-26a的表达与GSK-3β呈负相关。这些数据表明,miR-26a通过直接调控Wnt/β-连环蛋白信号通路,在人类骨肉瘤细胞增殖中具有重要作用。

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