Analysis of TGF-beta signaling modulation by lung cancer specific transcription factors using ChIP-sequense

我们利用ChIP-seq和RNA-seq对肺腺癌细胞进行了全基因组分析，发现TTF-1是肺上皮细胞的主要调节因子，与Smad3相互作用，并在染色质上共定位。此外，TTF-1在Smad3上与Smad4竞争，抑制部分tgf - β信号传导，特别是emt相关基因的表达。在没有tgf - β刺激的情况下，TTF-1和Smad3也与染色质结合，并调节包括LMO3致癌基因在内的一些基因的表达。提出了tgf - β调控的新模型，以及tgf -1的抑瘤机制。这些数据将有助于开发新的肺腺癌治疗方法。这些结果作为原创文章发表在《细胞研究》杂志上。

We performed genome wide analysis using ChIP-seq and RNA-seq in lung adenocarcinoma cell lines, and we revealed TTF-1, which is the master regulator of lung epithelial cells, interact with Smad3, and co-localizes at the chromatin. Moreover, TTF-1 competes with Smad4 on Smad3, and inhibits part of TGF-beta signaling especially expression of EMT-related genes. TTF-1 and Smad3 also bind to the chromatin in the absence of TGF-beta stimulation, and regulate expression of some genes including LMO3 oncogene. We bring up new model of TGF-beta regulation, and tumor suppression mechanism of TTF-1.These data will contribute to development of new therapy of lung adenocarcinoma. These results are published in Cell Research as an original article.