SMAD7 and SERPINE1 as novel dynamic network biomarkers detect and regulate the tipping point of TGF-beta induced EMT  

SMAD7和SERPINE1作为新的动态网络生物标记物可检测并调控由TGF-β诱导的上皮间质转化过程临界点

作　　者：Zhonglin Jiang Lina Lu Yuwei Liu Si Zhang Shuxian Li Guanyu Wang Peng Wang Luonan Chen 姜钟琳;卢丽娜;刘雨薇;张思;李淑娴;王冠宇;王鹏;陈洛南(Key Laboratory of Systems Biology,Center for Excellence in Molecular Cell Science,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China;Bio-med Big Data Center,Key Laboratory of Computational Biology,CAS-MPG Partner Institute of Computational Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China;Institute of Biomedical Sciences and School of Life Sciences,East China Normal University,Shanghai 200241,China;Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming 650223,China;School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China;Guangdong Provincial Key Laboratory of Cell Microenviroment and Disease Research,Guangdong Provincial Key Laboratory of Computational Science and Material Design,Department of Biology,Southern University of Science and Technology,Shenzhen 518055,China;Laboratory of Systems Biology,Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 200031,China)

机构地区：[1]Key Laboratory of Systems Biology,Center for Excellence in Molecular Cell Science,Institute of Biochemistry and Cell Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,University of Chinese Academy of Sciences,Shanghai 200031,China [2]Bio-med Big Data Center,Key Laboratory of Computational Biology,CAS-MPG Partner Institute of Computational Biology,Shanghai Institutes for Biological Sciences,Chinese Academy of Sciences,Shanghai 200031,China [3]Institute of Biomedical Sciences and School of Life Sciences,East China Normal University,Shanghai 200241,China [4]Center for Excellence in Animal Evolution and Genetics,Chinese Academy of Sciences,Kunming 650223,China [5]School of Life Science and Technology,ShanghaiTech University,Shanghai 201210,China [6]Guangdong Provincial Key Laboratory of Cell Microenviroment and Disease Research,Guangdong Provincial Key Laboratory of Computational Science and Material Design,Department of Biology,Southern University of Science and Technology,Shenzhen 518055,China [7]Laboratory of Systems Biology,Shanghai Advanced Research Institute,Chinese Academy of Sciences,Shanghai 200031,China

出　　处：《Science Bulletin》2020年第10期842-853,M0004,共13页科学通报（英文版）

基　　金：supported by the National Key Research and Development Program of China (2017YFA0505500);the National Natural Science Foundation of China (31930022, 31771476, 61773196);Shanghai Municipal Science and Technology Major Project (2017SHZDZX01);Key Project of Zhangjiang National Innovation Demonstration Zone Special Development Fund (ZJ2018ZD-013);Ministry of Science and Technology Project (2017YFC0907505);Guangdong Provincial Key Laboratory Funds (2017B030301018, 2019B030301001);Shenzhen Research Funds (JCYJ20170307104535585, ZDSYS20140509142721429);Shenzhen Peacock Plan (KQTD2016053117035204)

摘　　要：Epithelial–mesenchymal transition(EMT) is a complex nonlinear biological process that plays essential roles in fundamental biological processes such as embryogenesis, wounding healing, tissue regeneration,and cancer metastasis. A hallmark of EMT is the switch-like behavior during state transition, which is characteristic of phase transitions. Hence, detecting the tipping point just before mesenchymal state transition is critical for understanding molecular mechanism of EMT. Through dynamic network biomarkers(DNB) model, a DNB group with 37 genes was identified which can provide the early-warning signals of EMT. Particularly, we found that two DNB genes, i.e., SMAD7 and SERPINE1 promoted EMT by switching their regulatory network which was further validated by biological experiments. Survival analyses revealed that SMAD7 and SERPINE1 as DNB genes further acted as prognostic biomarkers for lung adenocarcinoma.上皮间质转化(EMT)是一个复杂的非线性生物过程,在胚胎发生、伤口创伤愈合、组织再生和肿瘤转移等基本生物过程中发挥着重要作用.上皮间质转化以细胞状态转换时类似开关的行为为标志,该行为是相变的特征.因此,检测上皮细胞即将转为间质细胞前的临界点是理解上皮间质转化过程的分子机制的关键.通过动态网络标志物(DNB)模型,本文确定了一个拥有37个基因的DNB基因群;它可以提供上皮间质转化过程的早期预警信号.值得一提的是,本文研究发现SMAD7和SERPINE1这两个DNB基因通过切换它们的调控网络来促进EMT的发生;该发现被进一步的实验所证实.生存分析显示SMAD7和SERPINE1作为DNB基因.可用作肺腺癌的预后标志物.

关 键 词：Dynamic network biomarker Tipping point Epithelial–mesenchymal transition BISTABILITY Quantitative real-time PCR 

分 类 号：R34[医药卫生—基础医学] R73