Department of Spinal Surgery, Tianjin Hospital, Tianjin, P.R. China.
Oncol Res. 2018 Jul 5;26(6):837-846. doi: 10.3727/096504017X14920318811721. Epub 2017 Apr 12.
Abnormal expression of long noncoding RNAs (lncRNAs) often contributes to the unrestricted growth and invasion of cancer cells. lncRNA X-inactive specific transcript (XIST) expression is upregulated in several cancers; however, its underlying mechanism in osteosarcoma (OS) has not been elucidated. In the present study, we found that XIST expression was significantly increased in OS tissues and cell lines by LncRNA Profiler and qRT-PCR. The effects of XIST and miR-320b on OS cell proliferation and invasion were studied by MTT and Transwell invasion assays. The competing relationship between XIST and miR-320b was confirmed by luciferase reporter assay. Our results showed that XIST knockdown strikingly inhibited cell proliferation and invasion. Furthermore, XIST could directly bind to miR-320b and repress miR-320b expression. Moreover, XIST overexpression significantly relieved the inhibition on OS cell proliferation and invasion mediated by miR-320b overexpression, which involved the derepression of Ras-related protein RAP2B. We propose that XIST is responsible for OS cell proliferation and invasion and that XIST exerts its function through the miR-320b/RAP2B axis. Our findings suggest that lncRNA XIST may be a candidate prognostic biomarker and a target for new therapies in OS patients.
长链非编码 RNA（lncRNA）的异常表达通常导致癌细胞的不受控制的生长和侵袭。几种癌症中 X 染色体失活特异性转录物（XIST）的表达上调；然而，其在骨肉瘤（OS）中的潜在机制尚未阐明。在本研究中，我们通过 LncRNA Profiler 和 qRT-PCR 发现 XIST 在 OS 组织和细胞系中的表达显著增加。通过 MTT 和 Transwell 侵袭实验研究了 XIST 和 miR-320b 对 OS 细胞增殖和侵袭的影响。通过荧光素酶报告基因实验证实了 XIST 和 miR-320b 之间的竞争关系。我们的结果表明，XIST 敲低显着抑制细胞增殖和侵袭。此外，XIST 可以直接结合 miR-320b 并抑制 miR-320b 的表达。此外，XIST 的过表达显着缓解了 miR-320b 过表达介导的对 OS 细胞增殖和侵袭的抑制作用，这涉及 Ras 相关蛋白 RAP2B 的去抑制。我们提出 XIST 负责 OS 细胞的增殖和侵袭，并且 XIST 通过 miR-320b/RAP2B 轴发挥其功能。我们的研究结果表明，lncRNA XIST 可能是 OS 患者的候选预后生物标志物和新疗法的靶点。
