SMAD7 and SERPINE1 as novel dynamic network biomarkers detect and regulate the tipping point of TGF-beta induced EMT
SMAD7 and SERPINE1 as novel dynamic network biomarkers detect and regulate the tipping point of TGF-beta induced EMT
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SMAD7 和 SERPINE1 作为新型动态网络生物标志物检测和调节 TGF-β 诱导的 EMT 临界点
DOI：
10.1016/j.scib.2020.01.013
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发表时间：
2020-05-30
期刊：
影响因子：
18.9
通讯作者：
Chen, Luonan
中科院分区：
文献类型：
--
作者：
Jiang, Zhonglin;Lu, Lina;Chen, Luonan
上皮-间充质转化(EMT)是一个复杂的非线性生物学过程，在胚胎发生、创伤愈合、组织再生和肿瘤转移等基本生物学过程中发挥着重要作用。EMT的一个特点是在状态转变过程中表现出类似开关的行为，这是相变的特征。因此，检测间充质状态转变前的临界点对于理解EMT的分子机制至关重要。通过动态网络生物标记物(DNB)模型，确定了一个包含37个基因的DNB组，可以为EMT提供早期预警信号。特别是，我们发现两个DNB基因，即Smad7和SERPINE1，通过转换它们的调控网络来促进EMT，这一发现得到了生物学实验的进一步验证。生存分析表明，Smad7和SERPINE1作为DNB基因进一步成为肺腺癌预后的生物标志物。(C)2020年科学中国出版社。爱思唯尔出版社、科学中国出版社出版。版权所有。
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. (C) 2020 Science China Press. Published by Elsevier B.V. and Science China Press. All rights reserved.