Upregulation of Ying Yang 1 (YY1) suppresses esophageal squamous cell carcinoma development through heme oxygenase-1
Upregulation of Ying Yang 1 (YY1) suppresses esophageal squamous cell carcinoma development through heme oxygenase-1
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YY1 的上调通过血红素加氧酶 1 抑制食管鳞状细胞癌的发展
DOI：
10.1111/cas.12248
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发表时间：
2013-11-01
期刊：
影响因子：
5.7
通讯作者：
Zhang, Shuyu
中科院分区：
文献类型：
--
作者：
Luo, Judong;Zhou, Xifa;Zhang, Shuyu
食管鳞状细胞癌（ESCC）是世界上最致命的恶性肿瘤之一。Ying Yang 1（YY 1）是一种广泛表达的GLI-Kruppel锌指转录因子，在胚胎发育、生长、凋亡、分化和致癌转化等多种基本生物学过程中发挥调节作用。本研究旨在探讨YY 1在正常食管组织和食管鳞癌组织中的表达及其在食管鳞癌发生发展中的作用。结果发现，YY 1 mRNA在食管癌组织中的表达明显高于癌旁组织和正常食管组织。通过免疫组化进一步证实了YY 1在肿瘤样品中的表达增加。此外，YY 1的过表达赋予ESCC TE-1细胞放射抗性，并导致细胞增殖显着降低。因此，TE-1细胞中YY 1表达的小干扰RNA介导的沉默通过增强P21与细胞周期蛋白D1和CDK 4（已知介导细胞周期进程的蛋白质复合物）的结合而导致增殖增加。此外，除了P21，血红素加氧酶-1（HO-1）被确定为YY 1下游效应物，因为YY 1刺激HO-1在食管癌细胞中的表达。YY 1通过HO-1的转录介导生物学功能。HO-1的强制表达可适度抑制TE-1细胞的增殖。食管鳞癌组织中YY 1和HO-1的表达呈显著相关。综上所述，我们证明了YY 1在食管癌中的过表达，并确定HO-1为其靶点。
Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Ying Yang 1 (YY1), a ubiquitously expressed GLI-Kruppel zinc finger transcription factor, plays a regulatory role in a variety of fundamental biological processes, such as embryonic development, growth, apoptosis, differentiation and oncogenic transformation. The purpose of this study was to investigate the expression of YY1 in normal and cancerous esophageal tissues and its function in ESCC development. We found that the expression of YY1 mRNA was significantly increased in the tumor tissues, compared with the para-tissues or normal esophageal tissues. The increased expression of YY1 in tumor samples was further confirmed by immunohistochemistry. Furthermore, the overexpression of YY1 conferred radioresistance to the ESCC TE-1 cells and resulted in markedly reduced cell proliferation. Accordingly, the small interfering RNA-mediated silencing of YY1 expression in TE-1 cells resulted in increased proliferation by enhancing the binding of P21 to Cyclin D1 and CDK4, a protein complex known to mediate cell cycle progression. Moreover, besides P21, heme oxygenase-1 (HO-1) was identified as a YY1 downstream effector, as YY1 stimulated HO-1 expression in esophageal cancer cells. YY1 mediated biological function through transcription of HO-1. Forced expression of HO-1 could moderately suppress proliferation of TE-1 cells. The expression of YY1 significantly correlated with that of HO-1 in ESCC tissues. Taken together, we demonstrated overexpression of YY1 in esophageal carcinoma and identified HO-1 as its target.