Wang Yandan, Cheng Nan, Luo Junpeng
Department of Otorhinolaryngology, Huaihe Hospital of Henan University, Kaifeng, 475000, People's Republic of China.
Department of Oncology, Huaihe Hospital of Henan University, Kaifeng, 475000, People's Republic of China.
J Biochem Mol Toxicol. 2017 Jul;31(7). doi: 10.1002/jbt.21904. Epub 2017 Jan 24.
Many studies have demonstrated that upregulation of long non-coding RNA (lncRNA) antisense non-coding RNA in the INK4 locus (ANRIL) plays an oncogenic role in various tumors, including nasopharyngeal carcinoma (NPC). The aim of this study is to explore the effect of ANRIL in NPC progression and cisplatin (DDP)-induced cytotoxicity. The results showed that ANRIL was highly expressed and let-7a was downregulated in NPC tissues and cells. Luciferase assay revealed that ANRIL could negatively regulate miR-let-7a expression. ANRIL knockdown inhibited NPC cell proliferation and induced apoptosis, while anti-let-7a reversed these effects. Combination treatment of si-ANRIL and DDP led to a lower viability, a more DNA strand breaks damage and a higher comet tail length compared with any single treatment, whereas let-7a inhibitor abolished these effects. Furthermore, depletion of ANRIL exacerbated DDP-induced cytotoxicity in NPC cells in vivo. Taken together, these data indicated that knockdown of ANRIL represses tumorigenicity and enhances DDP-induced cytotoxicity via regulating microRNA let-7a in NPC cells, providing a promising therapeutic strategy for NPC patients.
许多研究表明，INK4基因座中的长链非编码RNA（lncRNA）反义非编码RNA（ANRIL）的上调在包括鼻咽癌（NPC）在内的各种肿瘤中发挥致癌作用。本研究的目的是探讨ANRIL在NPC进展和顺铂（DDP）诱导的细胞毒性中的作用。结果显示，NPC组织和细胞中ANRIL高表达，而let-7a下调。荧光素酶报告基因检测显示，ANRIL可负调控miR-let-7a的表达。敲低ANRIL可抑制NPC细胞增殖并诱导凋亡，而抗let-7a可逆转这些作用。与任何单一治疗相比，si-ANRIL和DDP联合治疗导致更低的活力、更多的DNA链断裂损伤和更长的彗星尾长，而let-7a抑制剂消除了这些作用。此外，体内敲低ANRIL可加剧DDP诱导的NPC细胞毒性。综上所述，这些数据表明，敲低ANRIL可通过调节NPC细胞中的微小RNA let-7a来抑制肿瘤发生并增强DDP诱导的细胞毒性，为NPC患者提供了一种有前景的治疗策略。
