Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer
Transcription factor Sp1 regulates expression of cancer-associated molecule CD147 in human lung cancer
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DOI：
10.1111/j.1349-7006.2010.01554.x
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发表时间：
2010-06-01
期刊：
影响因子：
5.7
通讯作者：
Chen, Zhi-Nan
中科院分区：
文献类型：
--
作者：
Kong, Ling-Min;Liao, Cheng-Gong;Chen, Zhi-Nan
CD147是一种新型的癌症相关生物标志物，在人类肺癌的侵袭和转移中发挥着重要作用。尽管 CD147 具有许多已知的功能，但人们对 CD147 转录调控知之甚少。在本研究中，我们探讨了CD147在人肺癌组织中的调控。超过 60% 的人类肺癌组织表达不同程度的高水平 CD147。然后，我们克隆了人类 CD147 基因的 5' 侧翼区域，并鉴定了位于 -108 至 -42 的关键启动子区域，其中包含一个 Sp1 结合位点，这对于上调 CD147 启动子活性至关重要。这些结果通过使用 RNAi 或光神霉素 A 处理阻断 Sp1 以及使用真核表达载体转染上调 Sp1 得到证实。与 CD147 转录激活一致，在过表达 CD147 的肺癌细胞系中检测到高水平的 Sp1 表达。染色质免疫沉淀分析显示，在CD147高表达的95-D中，与CD147低表达的SK-MES-1相比，更多的Sp1能够与CD147启动子结合。免疫组化检测CD147表达与Sp1表达水平呈显着正相关(r=0.831)。总的来说，我们的结果表明 Sp1 对于调节人类肺癌中的 CD147 基因表达至关重要。 （癌症科学 2010）。
CD147 is a novel cancer-associated biomarker that plays an important role in the invasion and metastasis of human lung cancer. In spite of its many known functions, little is known about CD147 transcriptional regulation. In this study, we explored the regulation of CD147 in human lung cancer tissues. Over 60% of the human lung cancer tissues expressed differential high levels of CD147. We then cloned the 5'-flanking region of the human CD147 gene and identified a critical promoter region at -108 to -42 which contained one binding site for Sp1, which was essential in up-regulating CD147 promoter activity. These results were proven by blocking Sp1 using RNAi or mithramycin A treatment and up-regulating Sp1 using transfection with eukaryotic expression vector. Consistent with the CD147 transcription activation, a high level of Sp1 expression was detected in lung cancer cell lines overexpressing CD147. Chromatin immunoprecipitation assay showed that much more Sp1 could bind to the CD147 promoter in 95-D with CD147 high expression than in SK-MES-1 with CD147 low expression. There was a significant positive correlation between CD147 expression and Sp1 expression level detected by immunohistochemistry (r = 0.831). Collectively, our results suggest that Sp1 is essential for regulating the CD147 gene expression in human lung cancer. (Cancer Sci 2010).