基于网络药理学的莫匹罗星抗结直肠癌潜在靶点及作用机制研究

Possible Targets and Mechanisms of Mupirocin Against Colorectal Cancer Based on Network Pharmacology

目的 基于网络药理学探讨莫匹罗星抗结直肠癌(CRC)的潜在靶点及作用机制。方法 通过SwissTargetPrediction数据库预测莫匹罗星作用靶点,通过GeneCard数据库获取CRC相关靶点,利用Venny平台筛选出二者交集靶点作为莫匹罗星抗CRC潜在靶点,并通过String数据库构建潜在靶点的蛋白—蛋白相互作用(Protein-protein interaction,PPI)网络,利用Cytoscape软件对PPI进行拓扑分析及可视化。将潜在靶点导入Metascape及Bioinformatics平台,进行GO和KEGG富集分析,构建热图,气泡图以及通路图。结果 获得了莫匹罗星抗CRC潜在作用靶点89个,其中关键靶点为JUN、PTGS2、SRC、STAT3、IL1B及CASP3。富集度较高的生物学过程、细胞组成及分子功能分别主要为细菌源性分子的反应、内溶酶体和蛋白激酶c活性等。莫匹罗星抗CRC的信号通路有TRP通道的炎症介质调节、HIF-1信号通路等。结论 莫匹罗星抗CRC可能机制包括抑制癌细胞增殖和诱导癌细胞凋亡、抗炎以及破坏癌细胞微环境等。

Objective To investigate the possible targets and mechanisms of mupirocin(MPC) against colorectal cancer(CRC) by network pharmacology. Methods The targets of mupirocin were predicted by the SwissTargetPrediction database, and the CRC-related targets were obtained from the GeneCard database. Using Venny platform to screen the intersection target of the two as the potential anti-CRC target of mupirocin,and the proteinprotein interaction network(PPI) of the potential targets was constructed through the String database. Cytoscape was used to analyze and visualize the PPI topology. Potential targets of MPC against CRC were imported into Metascape and Bioinformatics platforms, GO and KEGG enrichment analysis was conducted, and heat maps, bubble maps and pathway maps were built. Results 89 potential targets of mupirocin anti-CRC were obtained, among which the key targets were JUN, PTGS2, SRC, STAT3, IL1B and CASP3. The biological process, cellular composition and molecular function with high enrichment were mainly the reaction of bacterial-derived molecules, endolysosome and protein kinase c activity, etc. The signaling pathways of mupirocin against CRC include the regulation of inflammatory mediators of TRP channels and the HIF-1 signaling pathway, etc. Conclusion The anti-colorectal mechanisms of MPC include inhibiting cancer cell proliferation and inducing cancer cell apoptosis, anti-inflammatory, and destroying cancer cell microenvironment, etc.