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