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基于大规模数据集的分析，鉴定小檗碱作为治疗肾透明细胞癌和 COVID-19 的潜在策略。

Identification of berberine as a potential therapeutic strategy for kidney clear cell carcinoma and COVID-19 based on analysis of large-scale datasets.

机构信息

Department of Nephrology, Shenzhen Traditional Chinese Medicine Hospital, The Fourth Clinical Medical College of Guangzhou University of Chinese Medicine, Shenzhen, Guangdong, China.

Shenzhen Key Laboratory, Shenzhen University General Hospital, Shenzhen, Guangdong, China.

出版信息

Front Immunol. 2023 Mar 23;14:1038651. doi: 10.3389/fimmu.2023.1038651. eCollection 2023.

DOI:10.3389/fimmu.2023.1038651
PMID:37033923
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10076552/
Abstract

BACKGROUND: Regarding the global coronavirus disease 2019 (COVID)-19 pandemic, kidney clear cell carcinoma (KIRC) has acquired a higher infection probability and may induce fatal complications and death following COVID-19 infection. However, effective treatment strategies remain unavailable. Berberine exhibits significant antiviral and antitumour effects. Thus, this study aimed to provide a promising and reliable therapeutic strategy for clinical decision-making by exploring the therapeutic mechanism of berberine against KIRC/COVID-19. METHODS: Based on large-scale data analysis, the target genes, clinical risk, and immune and pharmacological mechanisms of berberine against KIRC/COVID-19 were systematically investigated. RESULTS: In total, 1,038 and 12,992 differentially expressed genes (DEGs) of COVID-19 and KIRC, respectively, were verified from Gene Expression Omnibus and The Cancer Genome Atlas databases, respectively, and 489 berberine target genes were obtained from official websites. After intersecting, 26 genes were considered potential berberine therapeutic targets for KIRC/COVID-19. Berberine mechanism of action against KIRC/COVID-19 was revealed by protein-protein interaction, gene ontology, and Kyoto Encyclopedia of Genes and Genomes with terms including protein interaction, cell proliferation, viral carcinogenesis, and the PI3K/Akt signalling pathway. In COVID-19 patients, ACOX1, LRRK2, MMP8, SLC1A3, CPT1A, H2AC11, H4C8, and SLC1A3 were closely related to disease severity, and the general survival of KIRC patients was closely related to ACOX1, APP, CPT1A, PLK1, and TYMS. Additionally, the risk signature accurately and sensitively depicted the overall survival and patient survival status for KIRC. Numerous neutrophils were enriched in the immune system of COVID-19 patients, and the lives of KIRC patients were endangered due to significant immune cell infiltration. Molecular docking studies indicated that berberine binds strongly to target proteins. CONCLUSION: This study demonstrated berberine as a potential treatment option in pharmacological, immunological, and clinical practice. Moreover, its therapeutic effects may provide potential and reliable treatment options for patients with KIRC/COVID-19.

摘要

背景： 全球 2019 年冠状病毒病（COVID-19）大流行期间，肾透明细胞癌（KIRC）的感染概率更高，COVID-19 感染后可能引发致命并发症和死亡。然而，目前尚无有效的治疗策略。小檗碱具有显著的抗病毒和抗肿瘤作用。因此，本研究旨在通过探讨小檗碱治疗 KIRC/COVID-19 的作用机制，为临床决策提供一种有前途且可靠的治疗策略。

方法： 基于大规模数据分析，系统研究了小檗碱治疗 KIRC/COVID-19 的靶基因、临床风险以及免疫和药理学机制。

结果： 分别从基因表达综合数据库和癌症基因组图谱数据库中验证了 COVID-19 和 KIRC 的 1038 个和 12992 个差异表达基因（DEG），并从小檗碱官方网站获得了 489 个小檗碱靶基因。经 intersect 后，得到 26 个 KIRC/COVID-19 的潜在小檗碱治疗靶基因。通过蛋白质-蛋白质相互作用、基因本体论和京都基因与基因组百科全书分析，揭示了小檗碱治疗 KIRC/COVID-19 的作用机制，包括蛋白质相互作用、细胞增殖、病毒致癌和 PI3K/Akt 信号通路。在 COVID-19 患者中，ACOX1、LRRK2、MMP8、SLC1A3、CPT1A、H2AC11、H4C8 和 SLC1A3 与疾病严重程度密切相关，KIRC 患者的总体生存率与 ACOX1、APP、CPT1A、PLK1 和 TYMS 密切相关。此外，风险特征准确且敏感地描绘了 KIRC 的总生存率和患者生存率。COVID-19 患者的免疫系统中富含大量中性粒细胞，而 KIRC 患者的生命则因显著的免疫细胞浸润而受到威胁。分子对接研究表明，小檗碱与靶蛋白结合牢固。

结论： 本研究表明小檗碱是一种有潜力的治疗选择，可用于药理学、免疫学和临床实践。此外，其治疗效果可能为 KIRC/COVID-19 患者提供潜在且可靠的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/b88657462ffd/fimmu-14-1038651-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/fadacd2626c1/fimmu-14-1038651-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/beb5f0a99059/fimmu-14-1038651-g002.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/faff78cabb33/fimmu-14-1038651-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/08890d49ebf2/fimmu-14-1038651-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/bebad8535452/fimmu-14-1038651-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/8644884d35e5/fimmu-14-1038651-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/b88657462ffd/fimmu-14-1038651-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/fadacd2626c1/fimmu-14-1038651-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/beb5f0a99059/fimmu-14-1038651-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/24a76ff541ed/fimmu-14-1038651-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/8c27dca53a3a/fimmu-14-1038651-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/faff78cabb33/fimmu-14-1038651-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/08890d49ebf2/fimmu-14-1038651-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/bebad8535452/fimmu-14-1038651-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/8644884d35e5/fimmu-14-1038651-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e72e/10076552/b88657462ffd/fimmu-14-1038651-g009.jpg

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本文引用的文献

[1]
Efficacy of Cabozantinib in Metastatic MiT Family Translocation Renal Cell Carcinomas.

Oncologist. 2022-12-9

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