Significance of the NOR1-FOXA1/HDAC2-Slug regulatory network in epithelial-mesenchymal transition of tumor cells.
Significance of the NOR1-FOXA1/HDAC2-Slug regulatory network in epithelial-mesenchymal transition of tumor cells.
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NOR1-FOXA1/HDAC2-Slug 调控网络在肿瘤细胞上皮间质转化中的意义。
DOI：
10.18632/oncotarget.7778
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发表时间：
2016-03-29
期刊：
影响因子：
--
通讯作者：
Xiang B
中科院分区：
文献类型：
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作者：
Wang W;Yi M;Chen S;Li J;Li G;Yang J;Zheng P;Zhang H;Xiong W;McCarthy JB;Li G;Li X;Xiang B
上皮-间充质转化(EMT)过程被认为在鼻咽癌(NPC)的进展中起着关键作用，NPC是一种头颈部鳞状细胞癌，有早期转移的趋势。目前，EMT参与鼻咽癌进展的诱导者受到了很大关注，而拮抗剂的研究还不是很深入。在这项研究中，利用从鼻咽癌样本中获得的全球基因表达谱的数据挖掘，对EMT相关基因表达模式进行了无偏分析，从而成功地识别了Nor1、FOXA1和SLUG，所有这些基因在鼻咽癌进展过程中都表现出异常表达。采用异位表达和RNA干扰的方法，研究肿瘤抑制基因Nor1对鼻咽癌细胞在鼻咽癌EMT过程中的作用。Nor1在鼻涕虫诱导的EMT中抑制肿瘤的分子机制被认为依赖于Nor1与FOXA1-HDAC2复合体的合作。我们还发现FOXA1和HDAC2结合了slug启动子，并直接抑制了其转录。我们的数据揭示了Nor1-FOXA1/HDAC2-slug网络在调控鼻咽癌EMT过程和侵袭性方面先前未被认识到的作用。
The epithelial-mesenchymal transition (EMT) process is believed to play a crucial role in nasopharyngeal carcinoma (NPC) progression, a squamous cell carcinoma of the head and neck with the tendency to metastasize early. At present, much attention has been given to the inducer of EMT involved in NPC progression, while antagonists have been less intensively characterized. In this study, unbiased analysis of EMT-associated gene expression patterns was performed using data mining of global gene expression profiles derived from NPC samples, leading to the successful identification of NOR1, FOXA1, and Slug, all of which showed aberrant expression during NPC progression. The effect of tumor suppressor NOR1 on Slug-induced NPC cells during the EMT process was investigated by use of ectopic expression and RNA interference methods. The molecular mechanisms underlying the tumor-suppressing effect of NOR1 on Slug-induced EMT were thought to be dependent on the cooperation of NOR1 with the FOXA1-HDAC2 complex. We also showed that FOXA1 and HDAC2 bind the slug promoter and directly repress its transcription. Our data revealed a previously unrecognized role of the NOR1-FOXA1/HDAC2-Slug network in the regulation of the EMT process and aggressiveness of NPC.