Background Colorectal cancer(CRC)is a type of malignant gastroenteric tumors associated with a high mortal-ity rate worldwide.Calycosin,a natural phytoestrogen,possesses potent anti-cancer properties.We structurally m...Background Colorectal cancer(CRC)is a type of malignant gastroenteric tumors associated with a high mortal-ity rate worldwide.Calycosin,a natural phytoestrogen,possesses potent anti-cancer properties.We structurally modified calycosin to improve its physicochemical properties,and generated a novel small molecule termed CA028.Methods By using network pharmacology,followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis and molecular docking,we aimed to predict and disclose the biological functions and mechanism of CA028 in the treatment of CRC through bioinformatic analyses.Results By searching the online Swiss Target Prediction and TargetNet databases,we identified 150 genes shared by CA028 and CRC.Using the Search Tool for the Retrieval of Interacting Genes(STRING)database and Cytoscape software,we identified 14 hub-functional genes,namely the FYN proto-oncogene,a Src family tyrosine kinase(F YN),mitogen-activated protein kinase 1(MAPK1),MAPK8,MAPK14,Rac family small GTPase 1(RAC1),epi-dermal growth factor receptor(EGFR),protein tyrosine kinase 2(PTK2),sphingosine-1-phosphate receptor 1(S1PR1),S1PR2,Janus kinase 1(JAK1),JAK2,the RELA proto-oncogene NF-𝜅B subunit(RELA),bradykinin re-ceptor B1(BDKRB1),and BDKRB2.Additionally,biological docking analysis using the Autodock Vina software revealed that FYN and MAPK1 were the main pharmacological proteins of CA028 against CRC.The gene ontol-ogy analysis using R-language packages further revealed the anti-CRC functions of CA028,including biological processes,cell components,and molecular pathways.Conclusion CA028 exhibits effective pharmacological activity against CRC by suppressing the proliferation of CRC cells and improving the tumor microenvironment.Importantly,certain predicted genes(e.g.,FYN and MAPK1)may be the pharmacological targets of CA028 in the treatment of CRC.展开更多
基金the National Natural Science Founda-tion of China(Grant Nos.81973574,82174082,and 82060736)Guangxi Natural Science Foundation(Grant Nos.2019GXNSFFA245001 and 2018GXNSFAA281334)Innovation Project of Guangxi Graduate Education(Grant No.YCSW2021253).
文摘Background Colorectal cancer(CRC)is a type of malignant gastroenteric tumors associated with a high mortal-ity rate worldwide.Calycosin,a natural phytoestrogen,possesses potent anti-cancer properties.We structurally modified calycosin to improve its physicochemical properties,and generated a novel small molecule termed CA028.Methods By using network pharmacology,followed by gene ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analysis and molecular docking,we aimed to predict and disclose the biological functions and mechanism of CA028 in the treatment of CRC through bioinformatic analyses.Results By searching the online Swiss Target Prediction and TargetNet databases,we identified 150 genes shared by CA028 and CRC.Using the Search Tool for the Retrieval of Interacting Genes(STRING)database and Cytoscape software,we identified 14 hub-functional genes,namely the FYN proto-oncogene,a Src family tyrosine kinase(F YN),mitogen-activated protein kinase 1(MAPK1),MAPK8,MAPK14,Rac family small GTPase 1(RAC1),epi-dermal growth factor receptor(EGFR),protein tyrosine kinase 2(PTK2),sphingosine-1-phosphate receptor 1(S1PR1),S1PR2,Janus kinase 1(JAK1),JAK2,the RELA proto-oncogene NF-𝜅B subunit(RELA),bradykinin re-ceptor B1(BDKRB1),and BDKRB2.Additionally,biological docking analysis using the Autodock Vina software revealed that FYN and MAPK1 were the main pharmacological proteins of CA028 against CRC.The gene ontol-ogy analysis using R-language packages further revealed the anti-CRC functions of CA028,including biological processes,cell components,and molecular pathways.Conclusion CA028 exhibits effective pharmacological activity against CRC by suppressing the proliferation of CRC cells and improving the tumor microenvironment.Importantly,certain predicted genes(e.g.,FYN and MAPK1)may be the pharmacological targets of CA028 in the treatment of CRC.
