The Otolaryngological Department, Meizhou People's Hospital, Meizhou, Guangdong, P.R. China.
State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, P.R. China.
Sci Rep. 2018 Feb 20;8(1):3333. doi: 10.1038/s41598-018-21708-z.
Recent molecularly targeted approaches have gained advances in nasopharyngeal carcinoma treatment. However, the estimated five-year survival rate has not met the desired degree of improvement. Here, we report that upregulation of the expression of the SOX2-activated lncRNA ANRIL is involved in nasopharyngeal carcinoma. ANRIL has been found to be upregulated in clinical nasopharyngeal carcinoma. Using genetic approaches targeting ANRIL in nasopharyngeal carcinoma cells, we found that the knockdown of ANRIL inhibits cell proliferation in vitro and in vivo. Mechanistically, SOX2 binds with ANRIL and increases its RNA level, which upregulates β-catenin signalling, resulting in enhanced nasopharyngeal carcinoma tumourigenesis. Expression levels of ANRIL are positively correlated with SOX2 and β-catenin in clinical nasopharyngeal carcinoma samples. Our findings demonstrate that the SOX2-ANRIL-β-catenin axis plays a critical role in nasopharyngeal carcinoma proliferation and provide a potential therapeutic approach for nasopharyngeal carcinoma patients.
近年来，分子靶向治疗在鼻咽癌治疗方面取得了进展。然而，估计五年生存率仍未达到预期的改善程度。在这里，我们报告 SOX2 激活的长非编码 RNA ANRIL 的表达上调与鼻咽癌有关。已经发现 ANRIL 在临床鼻咽癌中上调。通过针对鼻咽癌细胞中 ANRIL 的遗传方法，我们发现 ANRIL 的敲低抑制了体外和体内的细胞增殖。在机制上，SOX2 与 ANRIL 结合并增加其 RNA 水平，从而上调 β-连环蛋白信号，导致增强的鼻咽癌肿瘤发生。临床鼻咽癌样本中 ANRIL 的表达水平与 SOX2 和 β-连环蛋白呈正相关。我们的研究结果表明，SOX2-ANRIL-β-连环蛋白轴在鼻咽癌增殖中起着关键作用，并为鼻咽癌患者提供了一种潜在的治疗方法。
