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微小RNA-198通过直接靶向ROCK1抑制人骨肉瘤的肿瘤行为。

MicroRNA-198 inhibited tumorous behaviors of human osteosarcoma through directly targeting ROCK1.

作者信息

Zhang Shilian, Zhao Yuehua, Wang Lijie

机构信息

Department of Pediatrics, Affiliated Hospital of Weifang Medical University, China.

Department of Pediatrics, Affiliated Hospital of Weifang Medical University, China.

出版信息

Biochem Biophys Res Commun. 2016 Apr 8;472(3):557-65. doi: 10.1016/j.bbrc.2016.03.040. Epub 2016 Mar 10.

Abstract

Osteosarcoma is an aggressive primary sarcoma of bone and occurs mainly in adolescents and young adults. The prognosis of OS remains poor, and most of them will die due to local relapse or metastases. The discovery of microRNAs provides a new possibility for the early diagnosis and treatment of OS. Thus, the aim of this study was to explore the expression and functions of microRNA-198 (miR-198) in osteosarcoma. The expression levels of miR-198 were determined by qRT-PCR in osteosarcoma tissues and cell lines. Cell proliferation assays, migration and invasion assays were adopted to investigate the effects of miR-198 on tumorous behaviors of osteosarcoma cells. The results showed that miR-198 expression levels were lower in osteosarcoma tissues and cell lines. In addition, low miR-198 expression levels were correlated with TNM stage and distant metastasis. After miR-198 mimics transfection, cell proliferation, migration and invasion were significantly suppressed in the osteosarcoma cells. Furthermore, ROCK1 was identified as a novel direct target of miR-198 in osteosarcoma. These findings suggested that miR-198 may act not only as a novel prognostic marker, but also as a potential target for molecular therapy of osteosarcoma.

摘要

骨肉瘤是一种侵袭性原发性骨肉瘤,主要发生于青少年和青年。骨肉瘤的预后仍然很差,大多数患者会因局部复发或转移而死亡。微小RNA的发现为骨肉瘤的早期诊断和治疗提供了新的可能性。因此,本研究旨在探讨微小RNA-198(miR-198)在骨肉瘤中的表达及功能。采用qRT-PCR检测骨肉瘤组织和细胞系中miR-198的表达水平。采用细胞增殖实验、迁移和侵袭实验研究miR-198对骨肉瘤细胞肿瘤行为的影响。结果显示,骨肉瘤组织和细胞系中miR-198表达水平较低。此外,miR-198低表达水平与TNM分期及远处转移相关。转染miR-198模拟物后,骨肉瘤细胞的增殖、迁移和侵袭能力均受到显著抑制。此外,ROCK1被鉴定为骨肉瘤中miR-198的一个新的直接靶点。这些发现表明,miR-198不仅可能作为一种新的预后标志物,还可能作为骨肉瘤分子治疗的潜在靶点。

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