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长链非编码RNA NBAT1通过抑制miR-21负向调节骨肉瘤细胞的生长和转移。

Long noncoding RNA NBAT1 negatively modulates growth and metastasis of osteosarcoma cells through suppression of miR-21.

作者信息

Yang Cheng, Wang Guijiang, Yang Jian, Wang Liguo

机构信息

No.4 Department of Orthopedics, Cangzhou Central HospitalCangzhou 061001, Hebei Province, China.

出版信息

Am J Cancer Res. 2017 Oct 1;7(10):2009-2019. eCollection 2017.

Abstract

Osteosarcoma (OS) is the most common primary bone malignancies. Long noncoding RNAs (lncRNAs) are key regulatory RNAs which takes part in several biological processes. LncRNA neuroblastoma associated transcript 1 (NBAT1) is a newly identified functional lncRNA. NBAT1 functions as a tumor suppressor in some cancers. However, the expression pattern, the biological function and the mechanisms of NBAT1 in OS progress have not been elucidated. In this study, for the first time, we found that NBAT1 expression is downregulated in OS tissues and cell lines and is associated with clinical stage, distant metastasis and poor prognosis. Loss- and gain-of-function assays showed that NBAT1 played a negative regulatory role in OS growth and metastasis and . Further investigation demonstrated that NBAT1 physically interacted with miR-21 and then suppressed its expression. NBAT1 also regulated downstream genes targeted by miR-21, including and . These findings may extend the function of NBAT1 in tumor progression and provide a novel target for OS treatment.

摘要

骨肉瘤(OS)是最常见的原发性骨恶性肿瘤。长链非编码RNA(lncRNAs)是参与多种生物学过程的关键调控RNA。LncRNA神经母细胞瘤相关转录本1(NBAT1)是一种新发现的功能性lncRNA。NBAT1在某些癌症中起肿瘤抑制作用。然而,NBAT1在骨肉瘤进展中的表达模式、生物学功能及机制尚未阐明。在本研究中,我们首次发现NBAT1在骨肉瘤组织和细胞系中表达下调,且与临床分期、远处转移及预后不良相关。功能缺失和功能获得实验表明,NBAT1在骨肉瘤的生长和转移中起负性调节作用。进一步研究表明,NBAT1与miR-21直接相互作用并抑制其表达。NBAT1还调控miR-21靶向的下游基因,包括……这些发现可能扩展了NBAT1在肿瘤进展中的功能,并为骨肉瘤治疗提供了新的靶点。

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