Department of Otorhinolaryngology Head and Neck Surgery, Taizhou People's Hospital, Taizhou 225300, Jiangsu, PR China.
Oncol Rep. 2012 Dec;28(6):2101-6. doi: 10.3892/or.2012.2027. Epub 2012 Sep 12.
Let-7a is frequently downregulated in various types of human cancer including nasopharyngeal carcinoma. However, the underlying mechanism of let-7a action in nasopharyngeal carcinoma remains elusive. In this study, we show that the enhancer of zeste homolog 2 (EZH2) is a direct target of let-7a in human nasopharyngeal carcinoma cells. The inhibition of EZH2 in vitro by let-7a, EZH2 siRNA, attenuated nasopharyngeal carcinoma cell growth, inhibited cell proliferation and induced cell apoptosis. In addition, for each biological process we identified ontology-associated transcripts that significantly correlate with EZH2 expression. Finally, the expression of EZH2 significantly abrogated let-7a-mediated cell proliferation and apoptosis in the nasopharyngeal carcinoma cells. Taken together, our results suggest that let-7a and EZH2 may be potential therapeutic targets for nasopharyngeal carcinoma.
Let-7a 在包括鼻咽癌在内的各种人类癌症中经常下调。然而，Let-7a 在鼻咽癌中的作用的潜在机制仍不清楚。在这项研究中，我们表明，EZH2 是人类鼻咽癌细胞中 Let-7a 的直接靶标。Let-7a、EZH2 siRNA 在体外抑制 EZH2，可减弱鼻咽癌细胞生长，抑制细胞增殖并诱导细胞凋亡。此外，对于我们鉴定的每个与生物学过程相关的转录本，其与 EZH2 表达显著相关。最后，EZH2 的表达显著消除了 Let-7a 介导的鼻咽癌细胞增殖和凋亡。总之，我们的研究结果表明，Let-7a 和 EZH2 可能是鼻咽癌的潜在治疗靶点。
