Department of Orthopaedics, First Affiliated Hospital of Dalian Medical University, Dalian, Liaoning 116044, China.
Laboratory of Pathogenic Biology, College of Basic Medical Science of Dalian Medical University, Dalian 116027, China.
Cancer Lett. 2016 Nov 28;382(2):137-146. doi: 10.1016/j.canlet.2016.08.024. Epub 2016 Sep 5.
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 miR-645-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.
化疗不敏感仍然是骨肉瘤治疗的主要障碍。最近，越来越多的证据表明，长非编码 RNA（lncRNA）在肿瘤发生中起着重要作用。然而，对于新型 lncRNA 对顺铂治疗的潜在生物学作用和调节机制知之甚少。在这里，我们发现 lncRNA LINC00161 被顺铂诱导在骨肉瘤细胞中。升高的 LINC00161 通过上调 IFIT2 增加顺铂诱导的细胞凋亡并逆转骨肉瘤细胞的顺铂耐药表型。进一步的机制研究表明，LINC00161 可以海绵吸附内源性 miR-645 并抑制其活性，导致 IFIT2 增加。此外，我们确定 LINC00161 通过调节 miR-645-IFIT2 通路增强顺铂诱导的细胞凋亡。因此，这些发现表明 LINC00161 是顺铂诱导细胞凋亡的重要调节因子，LINC00161-miR-645-IFIT2 信号轴在降低骨肉瘤化疗耐药性方面起着重要作用。
