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LncRNA THOR attenuates cisplatin sensitivity of nasopharyngeal carcinoma cells via enhancing cells stemness
Biochimie ( IF 3.3 ) Pub Date : 2018-06-26 , DOI: 10.1016/j.biochi.2018.06.015
Ling Gao , Xiu-lian Cheng , Hua Cao

The roles and mechanisms of long non-coding RNAs (lncRNA) in nasopharyngeal carcinoma (NPC) cells stemness and chemotherapeutic sensitivity are unclear. Here, Quantitative real-time PCR (qRT-PCR) was performed to detect the lncRNA THOR expression in NPC and normal adjacent tissues, adherent NPC cells and non-adherent NPC spheres, and we found that THOR was significantly increased in NPC tissues and non-adherent NPC spheres. Further in vitro and in vivo experiments were carried out and identified that knockdown of THOR attenuated NPC cells stemness, characterized as the decrease of spheres formation ability, cell proliferation, migration, invasion, stemness markers expression and tumor initiation, and enhanced cisplatin sensitivity of NPC cells. Mechanistically, RNA immunoprecipitation (RIP), immunofluorescence and luciferase reporter analysis indicated that THOR could enhance YAP transcriptional activity via directly binding to YAP and suppressing its translocation from nuclear to cytoplasm. Notably, overexpression of YAP rescued the inhibition of THOR knockdown on NPC cells and spheres stemness and promotion on cisplatin sensitivity. Thus, our results demonstrate that lncRNA THOR could attenuate cisplatin sensitivity of NPC cells by enhancing cells stemness through promoting YAP transcriptional activity.



中文翻译:

LncRNA THOR通过增强细胞干性来减弱鼻咽癌细胞的顺铂敏感性

长期非编码RNA(lncRNA)在鼻咽癌(NPC)细胞干性和化学敏感性中的作用和机制尚不清楚。在这里,进行了实时定量PCR(qRT-PCR),以检测NPC和正常邻近组织,粘附的NPC细胞和非粘附的NPC球中的lncRNA THOR表达,我们发现THOR在NPC组织和非NPC组织中显着增加贴附的NPC球体。进一步的体外体内进行了实验,发现敲除THOR可减弱NPC细胞的干性,其特征是降低了球形成能力,细胞增殖,迁移,侵袭,干性标志物表达和肿瘤起始,并增强了NPC细胞的顺铂敏感性。从机理上讲,RNA免疫沉淀(RIP),免疫荧光和荧光素酶报告基因分析表明THOR可通过直接与YAP结合并抑制其从核到细胞质的转运来增强YAP转录活性。值得注意的是,YAP的过表达挽救了对NPC细胞和球体干细胞抑制THOR的抑制作用并促进了顺铂敏感性。因此,

更新日期:2018-06-26
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