Huang Tonghai, Wang Guangsuo, Yang Lin, Peng Bin, Wen Yuxin, Ding Guanggui, Wang Zheng
Department of Thoracic Surgery, Shenzhen People's Hospital , Shenzhen, People's Republic of China .
DNA Cell Biol. 2017 Nov;36(11):947-958. doi: 10.1089/dna.2017.3857. Epub 2017 Oct 3.
Lung cancer is the leading cause of cancer-related death worldwide. Despite the advancement in surgery and chemotherapy, the prognosis of patients with advanced lung cancer is still poor. Yin Yang-1 (YY1) is a multifunctional transcription factor that exhibits positive and negative control on a large number of cellular and viral genes. In this study, we showed that the expression of YY1 is upregulated in lung cancer tissues as compared to adjacent normal tissues. Patients with higher expression of YY1 had larger tumor size, poor differentiation, higher TNM stage, and lymph node metastasis. Ectopic expression of YY1 in lung cancer cells promoted cell proliferation and invasion. Inversely, siRNA-mediated silencing of YY1 inhibited cell proliferation and induced apoptosis. These results suggested that YY1 may function as an oncogene in lung cancer. Moreover, through luciferase reporter assay, electrophoretic mobility shift assay, and chromatin immunoprecipitation assay, we showed that YY1 could directly bind to the promoter region of (long noncoding RNA-plasmacytoma variant translocation 1 [lncRNA-PVT1]) and activated its transcription through the consensus YY1 motif. Knockdown of the expression of YY1 reduced cell proliferation in vivo, consistent with the results obtained from silencing the expression of YY1 in lung cancer cells. Collectively, our study showed a critical role of YY1 in the regulation of tumorigenesis, partly through its downstream target PVT1.
肺癌是全球癌症相关死亡的主要原因。尽管手术和化疗取得了进展，但晚期肺癌患者的预后仍然很差。阴阳-1（YY1）是一种多功能转录因子，对大量细胞和病毒基因具有正负调控作用。在本研究中，我们发现与相邻正常组织相比，肺癌组织中YY1的表达上调。YY1高表达的患者肿瘤体积更大、分化差、TNM分期更高且有淋巴结转移。肺癌细胞中YY1的异位表达促进细胞增殖和侵袭。相反，siRNA介导的YY1沉默抑制细胞增殖并诱导凋亡。这些结果表明YY1可能在肺癌中作为癌基因发挥作用。此外，通过荧光素酶报告基因检测、电泳迁移率变动分析和染色质免疫沉淀分析，我们发现YY1可以直接结合到（长链非编码RNA-浆细胞瘤变异易位1 [lncRNA-PVT1]）的启动子区域，并通过共有YY1基序激活其转录。YY1表达的敲低降低了体内细胞增殖，这与在肺癌细胞中沉默YY1表达所获得的结果一致。总体而言，我们的研究表明YY1在肿瘤发生调控中起关键作用，部分是通过其下游靶点PVT1实现的。
