研究动态
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Entrectinib是一种在宫颈癌中可能抑制骨桥蛋白(SPP1)的药物——综合生物信息学方法。

Entrectinib a Plausible Inhibitor for Osteopontin (SPP1) in Cervical Cancer-Integrated Bioinformatic Approach.

发表日期:2023 Apr 22
作者: Pavan Kumar Poleboyina, Manikandan Alagumuthu, Akbar Pasha, Doneti Ravinder, Deepthi Pasumarthi, Smita C Pawar
来源: GENES & DEVELOPMENT

摘要:

子宫颈癌是妇女死亡的主要原因之一,特别是在承担全球负担超过四分之一的发展中国家。分泌的磷酸化蛋白-1,也称为OPN(骨桥蛋白),是一种整合素结合的糖基磷酸化蛋白,在多种肿瘤中过表达。 OPN是一种类似趋化因子的钙化ECM相关蛋白,发挥着评估各种癌症的转移潜力的关键作用。然而,SPP1在肿瘤微环境中的作用以及与CC相关的信号通路仍不清楚。 在我们的研究中,从GEO数据库中获取了三个CC微阵列数据集(GSE9750,GSE46857和GSE67522)以识别差异表达的基因。通过Enrichr和ShinyGO进行富集分析,并使用String和Cytoscape创建PPI相互作用网络。 GEPIA数据集用于验证前10个中心基因,并使用MVD,PyRx和GROMACS进行虚拟筛选,对接和动态模拟研究以鉴定适合的抑制剂对抗OPN蛋白。我们的结果显示,三个数据集共有11个DEG,基因本体路径富集分析显示2个生物过程,即编程性细胞死亡和动物器官发育,是所有三个数据集中普遍影响的机制。对接和动态研究显示,Entrectinib对OPN蛋白显示出优异的结合亲和力。基于结果,我们得出结论,OPN是子宫颈癌中最上调的基因之一,Entrectinib成为有希望的潜在OPN抑制剂,可以遏制子宫颈癌的进展。方法步骤的示意图如图示。方法的示意图。 ©2023. 作者(S)在Springer Science + Business Media,LLC的专有许可下,属于Springer Nature的一部分。
Cervical cancer is one of the major causes of death in women, especially in developing countries bearing more than a quarter of the global burden. Secreted phosphoprotein-1, also known as OPN (osteopontin), is an integrin-binding glycophosphoprotein that is overexpressed in a variety of tumors. OPN is a chemokine-like calcified ECM-associated protein that plays a crucial role in evaluating the metastatic potential of various cancers. However, the role of SPP1 in the tumor microenvironment and associated signaling pathways in CC is still unclear. In our study, three CC microarray datasets (GSE9750, GSE46857, and GSE67522) were obtained from the GEO database to identify the differentially expressed genes. Enrichment analysis was carried out by Enrichr and ShinyGO and the PPI interaction network was created by using String and Cytoscape. GEPIA datasets were used to validate the top 10 hub genes, and virtual screening, docking, and dynamic simulation studies were used to identify a suitable inhibitor against the OPN protein using MVD, PyRx, and GROMACS respectively. Our results show that a total of 11 DEGs were common for three datasets and gene ontology pathway enrichment analysis revealed that 2 biological processes i.e. programmed cell death and animal organ development commonly affected mechanisms in all three datasets. Docking and dynamic studies revealed that Entrectinib showed excellent binding affinity against OPN protein. Based on the results, we conclude that OPN is one of the most upregulated genes in cervical cancer and Entrectinib emerges to be a promising potential OPN inhibitor to curtail cervical cancer progression. Schematic representation: The schematic representation of methodology steps is illustrated in the graphical abstract. Schematic representation of methodology.© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.