Hou Zhibo, Zhao Wei, Zhou Ji, Shen Lan, Zhan Ping, Xu Chunhua, Chang Cunjie, Bi Hui, Zou Jue, Yao Xin, Huang Ruimin, Yu Like, Yan Jun
First Department of Respiratory Medicine, Nanjing Chest Hospital, Nanjing 210029, Jiangsu, China; Clinical Center of Nanjing Respiratory Diseases and Imaging, Nanjing 210029, Jiangsu, China.
MOE Key Laboratory of Model Animal for Disease Study, Model Animal Research Center, Nanjing Biomedical Research Institute, Nanjing University, Nanjing 210061, Jiangsu, China.
Int J Biochem Cell Biol. 2014 Aug;53:380-8. doi: 10.1016/j.biocel.2014.06.004. Epub 2014 Jun 10.
Sox2 overlapping transcript (Sox2ot) is a long noncoding RNA (lncRNA), localized on human chromosome 3q26.33, which is frequently amplified in lung squamous cell carcinomas (SCCs). However, its roles in lung cancer remain under investigation. In this study, we found that Sox2ot was up-regulated over two folds in 53.01% of human primary lung cancers (44/83). The expression level of Sox2ot is significantly higher in SCCs than that in adenocarcinomas (ADCs) of the lung. Further study found high Sox2ot expression predicted poor survival in lung cancer patients (P=0.0053), implying Sox2ot is a novel prognostic factor. In two human lung cancer cell lines, HCC827 and SK-MES-1, knocking down Sox2ot inhibited cell proliferation by inducing G2/M arrest, with a concomitant decrease of cells in S phase. Reduced protein levels of Cyclin B1 and Cdc2 were also observed. Importantly, knocking down Sox2ot decreased EZH2 expression and reintroduction of EZH2 allowed Sox2ot knockdown cells progressed through G2/M phase, which correlates with the restoration of Cyclin B1 and Cdc2 expressions. Altogether, our data suggested that Sox2ot plays an important role in regulating lung cancer cell proliferation, and may represent a novel prognostic indicator for the disease.
Sox2重叠转录本（Sox2ot）是一种长链非编码RNA（lncRNA），定位于人类染色体3q26.33，在肺鳞状细胞癌（SCC）中经常扩增。然而，其在肺癌中的作用仍在研究中。在本研究中，我们发现53.01%的人类原发性肺癌（44/83）中Sox2ot上调了两倍以上。Sox2ot的表达水平在肺鳞状细胞癌中显著高于肺腺癌（ADC）。进一步研究发现，Sox2ot高表达预示肺癌患者预后不良（P=0.0053），这意味着Sox2ot是一种新的预后因素。在两种人类肺癌细胞系HCC827和SK-MES-1中，敲低Sox2ot通过诱导G2/M期阻滞抑制细胞增殖，同时S期细胞减少。还观察到细胞周期蛋白B1和Cdc2的蛋白水平降低。重要的是，敲低Sox2ot会降低EZH2的表达，重新引入EZH2可使敲低Sox2ot的细胞通过G2/M期，这与细胞周期蛋白B1和Cdc2表达的恢复相关。总之，我们的数据表明Sox2ot在调节肺癌细胞增殖中起重要作用，可能是该疾病的一种新的预后指标。
