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Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer

Berberine exhibits anticancer efficacy against a variety of malignancies, including breast cancer (BRCA). However, the underlying mechanism is ambiguous. This study sought to explore the targets and the probable mechanism of berberine regulating autophagy in BRCA through network pharmacology, bioinf...

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Autores principales: Huang, Bowan, Wen, Gengzhi, Li, Rujia, Wu, Minhua, Zou, Zhenning
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10489552/
https://www.ncbi.nlm.nih.gov/pubmed/37682166
http://dx.doi.org/10.1097/MD.0000000000035070
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author Huang, Bowan
Wen, Gengzhi
Li, Rujia
Wu, Minhua
Zou, Zhenning
author_facet Huang, Bowan
Wen, Gengzhi
Li, Rujia
Wu, Minhua
Zou, Zhenning
author_sort Huang, Bowan
collection PubMed
description Berberine exhibits anticancer efficacy against a variety of malignancies, including breast cancer (BRCA). However, the underlying mechanism is ambiguous. This study sought to explore the targets and the probable mechanism of berberine regulating autophagy in BRCA through network pharmacology, bioinformatics, and molecular docking. The targets of berberine and autophagy-modulated genes were derived from online databases, and the Cancer Genome Atlas database was used to identify the differentially expressed genes of BRCA. Then, through intersections, the autophagy-modulated genes regulated by berberine (AMGRBs) in BRCA were obtained. Next, we established a protein–protein interaction network using the Search Tool for the Retrieval of Interacting Genes database. Afterward, gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were employed to explore the targets’ biological functions. Additionally, molecular docking was conducted to verify the binding ability of berberine to the targets. Finally, to determine the prognostic value of AMGRBs in BRCA, we performed overall survival analyses. We identified 29 AMGRBs in BRCA, including CASP3, MTOR, AKT1, GSK3B, PIK3CA, and others. Gene ontology enrichment analysis showed that the AMGRBs in BRCA were associated with autophagy regulation, negative regulation of catabolic process, macroautophagy, and other biological processes. Kyoto encyclopedia of genes and genomes enrichment analyses indicated that AMGRBs in BRCA were involved in epidermal growth factor receptor tyrosine kinase inhibitor resistance, PI3K/Akt signaling pathway, JAK-STAT signaling pathway, and others. Molecular docking results proved that berberine had strong binding affinities with AMGRBs in BRCA. Survival analyses indicated that ATM, HTR2B, LRRK2, PIK3CA, CDK5, and IFNG were associated with the prognosis of BRCA. This study identified the targets and pathways of berberine for regulating autophagy in BRCA, which contributed to a better understanding of berberine’s function in BRCA and serve as a foundation and reference for further study and therapeutic application of berberine.
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spelling pubmed-104895522023-09-09 Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer Huang, Bowan Wen, Gengzhi Li, Rujia Wu, Minhua Zou, Zhenning Medicine (Baltimore) Research Article: Observational Study Berberine exhibits anticancer efficacy against a variety of malignancies, including breast cancer (BRCA). However, the underlying mechanism is ambiguous. This study sought to explore the targets and the probable mechanism of berberine regulating autophagy in BRCA through network pharmacology, bioinformatics, and molecular docking. The targets of berberine and autophagy-modulated genes were derived from online databases, and the Cancer Genome Atlas database was used to identify the differentially expressed genes of BRCA. Then, through intersections, the autophagy-modulated genes regulated by berberine (AMGRBs) in BRCA were obtained. Next, we established a protein–protein interaction network using the Search Tool for the Retrieval of Interacting Genes database. Afterward, gene ontology and Kyoto encyclopedia of genes and genomes enrichment analyses were employed to explore the targets’ biological functions. Additionally, molecular docking was conducted to verify the binding ability of berberine to the targets. Finally, to determine the prognostic value of AMGRBs in BRCA, we performed overall survival analyses. We identified 29 AMGRBs in BRCA, including CASP3, MTOR, AKT1, GSK3B, PIK3CA, and others. Gene ontology enrichment analysis showed that the AMGRBs in BRCA were associated with autophagy regulation, negative regulation of catabolic process, macroautophagy, and other biological processes. Kyoto encyclopedia of genes and genomes enrichment analyses indicated that AMGRBs in BRCA were involved in epidermal growth factor receptor tyrosine kinase inhibitor resistance, PI3K/Akt signaling pathway, JAK-STAT signaling pathway, and others. Molecular docking results proved that berberine had strong binding affinities with AMGRBs in BRCA. Survival analyses indicated that ATM, HTR2B, LRRK2, PIK3CA, CDK5, and IFNG were associated with the prognosis of BRCA. This study identified the targets and pathways of berberine for regulating autophagy in BRCA, which contributed to a better understanding of berberine’s function in BRCA and serve as a foundation and reference for further study and therapeutic application of berberine. Lippincott Williams & Wilkins 2023-09-08 /pmc/articles/PMC10489552/ /pubmed/37682166 http://dx.doi.org/10.1097/MD.0000000000035070 Text en Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC) (https://creativecommons.org/licenses/by-nc/4.0/) , where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal.
spellingShingle Research Article: Observational Study
Huang, Bowan
Wen, Gengzhi
Li, Rujia
Wu, Minhua
Zou, Zhenning
Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer
title Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer
title_full Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer
title_fullStr Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer
title_full_unstemmed Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer
title_short Integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer
title_sort integrated network pharmacology, bioinformatics, and molecular docking to explore the mechanisms of berberine regulating autophagy in breast cancer
topic Research Article: Observational Study
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10489552/
https://www.ncbi.nlm.nih.gov/pubmed/37682166
http://dx.doi.org/10.1097/MD.0000000000035070
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