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一种新型反义长链非编码RNA SATB2-AS1在骨肉瘤中过表达,并增加细胞增殖和生长。

A novel antisense long non-coding RNA SATB2-AS1 overexpresses in osteosarcoma and increases cell proliferation and growth.

作者信息

Liu Si-Hong, Zhu Jian-Wei, Xu Hui-Hua, Zhang Gui-Qiang, Wang Yan, Liu Ya-Min, Liang Jun-Bo, Wang Yu-Xuan, Wu Yong, Guo Qi-Feng

机构信息

Jinan University, Guangzhou,, 510632, People's Republic of China.

Department of Orthopaedics, Guangzhou First People's Hospital, Guangzhou Medical University, Guangzhou,, 510180, People's Republic of China.

出版信息

Mol Cell Biochem. 2017 Jun;430(1-2):47-56. doi: 10.1007/s11010-017-2953-9. Epub 2017 Feb 11.

Abstract

The knowledge regarding the importance of long non-coding RNAs (lncRNAs), a new class of genes, is very sparse in osteosarcoma. In the present study, we describe the expression profile of lncRNAs in osteosarcomas compared with paired adjacent non-cancerous tissue (n = 7) using microarray analysis. A total of 25,733 lncRNAs were identified in osteosarcoma; 1995 lncRNAs were consistently upregulated and 2226 lncRNAs were consistently under-regulated in all samples analyzed (≥2.0-fold, p < 0.05). We have validated three over-regulated and three under-regulated lncRNAs in patient samples (n = 7). The antisense transcript of SATB2 protein (SATB2-AS1) was identified as one of the upregulated lncRNAs. The SATB2-AS1 is a 3197-bp lncRNA on chromosome 2. This is the first report, where we have documented the increased expression of SATB2-AS1 in osteosarcoma patients and in human osteosarcoma cancer cell lines (U2OS, HOS, MG63). SATB2-AS1 expression was significantly higher in the metastatic tumors compared to non-metastatic tumors. In vitro gain and loss of function approaches demonstrated that SATB2-AS1 regulates cell cycle, cell proliferation, and cell growth. In addition, SATB2-AS1 affects the translational expression of SATB2 gene. Our data demonstrate that an antisense non-coding RNA regulates the expression of its sense gene, and increases the cell growth, therefore pointing the pivotal functions of SATB2-AS1 in osteosarcoma.

摘要

关于长链非编码RNA(lncRNAs)这一类新基因的重要性,在骨肉瘤方面的了解非常有限。在本研究中,我们使用微阵列分析描述了骨肉瘤中lncRNAs的表达谱,并与配对的相邻非癌组织(n = 7)进行比较。在骨肉瘤中总共鉴定出25,733个lncRNAs;在所有分析样本中(≥2.0倍,p < 0.05),1995个lncRNAs持续上调,2226个lncRNAs持续下调。我们在患者样本(n = 7)中验证了3个上调和3个下调的lncRNAs。SATB2蛋白的反义转录本(SATB2-AS1)被鉴定为上调的lncRNAs之一。SATB2-AS1是位于2号染色体上的一个3197 bp的lncRNA。这是第一份报告,我们记录了SATB2-AS1在骨肉瘤患者和人骨肉瘤癌细胞系(U2OS、HOS、MG63)中的表达增加。与非转移性肿瘤相比,SATB2-AS1在转移性肿瘤中的表达显著更高。体外功能获得和缺失方法表明,SATB2-AS1调节细胞周期、细胞增殖和细胞生长。此外,SATB2-AS1影响SATB2基因的翻译表达。我们的数据表明,一种反义非编码RNA调节其正义基因的表达,并促进细胞生长,因此指出了SATB2-AS1在骨肉瘤中的关键作用。

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