Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR-645-IFIT2 axis
Long non-coding RNA LINC00161 sensitises osteosarcoma cells to cisplatin-induced apoptosis by regulating the miR-645-IFIT2 axis
复制标题
长非编码RNA LINC00161通过调节miR-645-IFIT2轴使骨肉瘤细胞对顺铂诱导的细胞凋亡敏感
DOI：
10.1016/j.canlet.2016.08.024
复制
发表时间：
2016-11-28
期刊：
影响因子：
9.7
通讯作者：
Zhang, Weiguo
中科院分区：
文献类型：
--
作者：
Wang, Yuan;Zhang, Li;Zhang, Weiguo
化疗不敏感性仍然是骨肉瘤治疗的主要障碍。近年来，越来越多的证据表明，长链非编码RNA（lncRNA）在肿瘤发生中起着重要作用。然而，对新型lncRNA在顺铂治疗中的潜在生物学作用和调控机制知之甚少。在这里，我们发现lncRNA LINC 00161在骨肉瘤细胞中被顺铂诱导。LINC 00161升高增加顺铂诱导的细胞凋亡，并通过上调IFIT 2逆转骨肉瘤细胞的顺铂耐药表型。进一步的机制研究显示，LINC 00161可以海绵化内源性miR-645并抑制其活性，导致IFIT 2增加。此外，我们确定LINC 00161通过调节miR 645-IFIT 2通路增强顺铂诱导的细胞凋亡。因此，这些发现表明LINC 00161是顺铂诱导的细胞凋亡中的重要调节因子，LINC 00161-miR-645-IFIT 2信号传导轴在降低骨肉瘤化疗耐药性中起重要作用。(C)2016爱思唯尔爱尔兰有限公司版权所有。
Chemotherapeutic insensitivity remains a major obstacle to osteosarcoma treatment. Recently, increasing evidence has suggested that long non-coding RNAs (lncRNAs) play an essential role in tumourigenesis. However, the potential biological roles and regulatory mechanisms of novel lncRNAs in response to cisplatin treatment are poorly understood. Here, we found that lncRNA LINC00161 was induced by cisplatin in osteosarcoma cells. Elevated LINC00161 increased cisplatin-induced apoptosis and reversed the cisplatin-resistant phenotype of osteosarcoma cells by upregulating IFIT2. Further mechanistic studies revealed that LINC00161 could sponge endogenous miR-645 and inhibit its activity leading to IFIT2 increase. In addition, we identified that LINC00161 enhanced cisplatin-induced apoptosis through regulation of the miR645-IFIT2 pathway. Thus, these findings demonstrate that LINC00161 is an essential regulator in cisplatin-induced apoptosis, and the LINC00161-miR-645-IFIT2 signalling axis plays an important role in reducing osteosarcoma chemoresistance. (C) 2016 Elsevier Ireland Ltd. All rights reserved.