Protein interaction network analysis of TGF-β signalling pathway enabled EMT process to anticipate the anticancer activity of curcumin

Shivananda Kandagalla, S. Shekarappa, Bharath Basavapattana Rudresh, Pavan Gollapalli, M. Hanumanthappa
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引用次数: 3

Abstract

TGF-β signalling is a key mediator of epithelial to mesenchymal transition (EMT) process and its up-regulation is identified as a hallmark of metastasis. Since TGF-β signalling pathway is known as a key therapeutic target in the treatment of EMT enabled cancer and the study aims at identification of key EMT genes by gene annotation tools and protein interaction network (PIN) to analyse the regulatory dynamics of an interactome. Meanwhile, the potency of curcumin against TGF-β signalling was evaluated by network pharmacology approach. Resultantly, 15 genes were identified as key regulators of TGF-β signalling pathway and seven were shortlisted as leading curcumin targets. Cumulatively, both approaches have justified the role of targets. Thus, curcumin was subjected to molecular docking with targets using AutoDock Vina. Wherein, curcumin has shown significant binding energy with targets EP300 and JUN (-7.1 and -6.4 kcal/mol) respectively indicating the potential anticancer property.
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TGF-β信号通路的蛋白相互作用网络分析使EMT过程能够预测姜黄素的抗癌活性
TGF-β信号是上皮细胞向间质转化(EMT)过程的关键介质,其上调被认为是转移的标志。由于TGF-β信号通路被认为是治疗EMT致癌癌症的关键治疗靶点,本研究旨在通过基因注释工具和蛋白相互作用网络(PIN)鉴定关键EMT基因,分析相互作用组的调控动力学。同时,采用网络药理学方法评价姜黄素对TGF-β信号通路的抑制作用。结果,15个基因被鉴定为TGF-β信号通路的关键调控因子,7个基因被确定为姜黄素的主要靶点。累积起来,这两种方法都证明了目标的作用是合理的。因此,使用AutoDock Vina对姜黄素进行分子对接。其中,姜黄素与靶点EP300和JUN分别显示出显著的结合能(-7.1和-6.4 kcal/mol),表明姜黄素具有潜在的抗癌特性。
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