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miR-124在骨肉瘤中的肿瘤抑制作用。

The tumor suppressor role of miR-124 in osteosarcoma.

作者信息

Geng Shuo, Zhang Xiaojun, Chen Jie, Liu Xing, Zhang Hepeng, Xu Xiaoyan, Ma Yan, Li Baoxin, Zhang Yunqi, Bi Zhenggang, Yang Chenglin

机构信息

Department of Orthopedic Surgery, the First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang Prov., China.

Department of gynaecology and obstetrics, the First Affiliated Hospital of Harbin Medical University, Nangang District, Harbin, Heilongjiang Prov., China.

出版信息

PLoS One. 2014 Jun 27;9(6):e91566. doi: 10.1371/journal.pone.0091566. eCollection 2014.

Abstract

MicroRNAs have crucial roles in development and progression of human cancers, including osteosarcoma. Recent studies have shown that miR-124 was down-regulated in many cancers; however, the role of miR-124 in osteosarcoma development is unknown. In this study, we demonstrate that expression of miR-124 is significantly downregulated in osteosarcoma tissues and cell lines, compared to the adjacent tissues. The expression of miR-124 in the metastases osteosarcoma tissues was lower than that in non- metastases tissues. We identified and confirmed Rac1 as a novel, direct target of miR-124 using prediction algorithms and luciferase reporter gene assays. Overexpression of miR-124 suppressed Rac1 protein expression and attenuated cell proliferation, migration, and invasion and induced apoptosis in MG-63 and U2OS in vitro. Moreover, overexpression of Rac1 in miR-124-transfected osteosarcoma cells effectively rescued the inhibition of cell invasion caused by miR-124. Therefore, our results demonstrate that miR-124 is a tumor suppressor miRNA and suggest that this miRNA could be a potential target for the treatment of osteosarcoma in future.

摘要

微小RNA在包括骨肉瘤在内的人类癌症的发生和发展过程中发挥着关键作用。最近的研究表明,miR-124在许多癌症中表达下调;然而,miR-124在骨肉瘤发生中的作用尚不清楚。在本研究中,我们证明与相邻组织相比,miR-124在骨肉瘤组织和细胞系中的表达显著下调。转移的骨肉瘤组织中miR-124的表达低于非转移组织。我们使用预测算法和荧光素酶报告基因实验鉴定并证实Rac1是miR-124一个新的直接靶点。在体外,miR-124的过表达抑制了Rac1蛋白表达,减弱了MG-63和U2OS细胞的增殖、迁移和侵袭能力,并诱导了细胞凋亡。此外,在转染了miR-124的骨肉瘤细胞中过表达Rac1有效挽救了miR-124对细胞侵袭的抑制作用。因此,我们的结果表明miR-124是一种肿瘤抑制性微小RNA,并提示这种微小RNA可能成为未来骨肉瘤治疗的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9146/4074038/48e14631a807/pone.0091566.g001.jpg

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