黄连素在包括乳腺癌（BRCA）在内的各种恶性肿瘤中展示出抗癌活性。然而，其潜在机制尚不明确。本研究旨在通过网络药理学、生物信息学和分子对接技术，探讨黄连素在BRCA中调节自噬的靶标和可能的机制。黄连素和自噬调节基因的靶标来源于在线数据库，使用癌症基因组图谱数据库识别BRCA的差异表达基因。然后，通过交集获取BRCA中由黄连素调节的自噬调节基因（AMGRBs）。接下来，我们使用检索相互作用基因数据库建立了蛋白质相互作用网络。随后，利用基因本体论和基因组百科全书富集分析探索靶标的生物学功能。此外，进行分子对接实验证实黄连素与靶标的结合能力。最后，为确定AMGRBs在BRCA中的预后价值，我们进行了整体生存分析。我们在BRCA中鉴定了29个AMGRBs，包括CASP3、MTOR、AKT1、GSK3B、PIK3CA等。基因本体论富集分析显示，BRCA中的AMGRBs与自噬调节、降解过程的负调节、巨噬细胞自噬等生物过程相关。基因组百科全书富集分析表明，BRCA中的AMGRBs参与表皮生长因子受体酪氨酸激酶抑制剂耐药、PI3K/Akt信号通路、JAK-STAT信号通路等。分子对接结果证明黄连素与BRCA中的AMGRBs具有较强的结合亲和力。生存分析显示，ATM、HTR2B、LRRK2、PIK3CA、CDK5和IFNG与BRCA的预后相关。本研究确定了黄连素在BRCA中调节自噬的靶标和途径，有助于更好地理解黄连素在BRCA中的功能，并为进一步研究和黄连素的治疗应用提供了基础和参考。版权所有 © 2023 作者。由 Wolters Kluwer Health, Inc. 出版。

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.Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.