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An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma

Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes,...

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Autores principales: Mo, Zhuomao, Cao, Zhirui, Yu, Ling, Wang, Yongdan, Li, Pan, Lin, Youwu, Zhang, Shijun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785361/
https://www.ncbi.nlm.nih.gov/pubmed/33457419
http://dx.doi.org/10.1155/2020/8886914
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author Mo, Zhuomao
Cao, Zhirui
Yu, Ling
Wang, Yongdan
Li, Pan
Lin, Youwu
Zhang, Shijun
author_facet Mo, Zhuomao
Cao, Zhirui
Yu, Ling
Wang, Yongdan
Li, Pan
Lin, Youwu
Zhang, Shijun
author_sort Mo, Zhuomao
collection PubMed
description Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5.
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spelling pubmed-77853612021-01-14 An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma Mo, Zhuomao Cao, Zhirui Yu, Ling Wang, Yongdan Li, Pan Lin, Youwu Zhang, Shijun Biomed Res Int Research Article Aims. Abundant evidences in traditional Chinese medicine (TCM) supported the therapeutic value of herbal medicine Yinchen in hepatocellular carcinoma (HCC), but the underlying mechanism remains to be investigated. Main Methods. The intersection of immune gene set, module genes, HCC-associated genes, and target genes of Yinchen was employed for further analyses. The module genes were identified by weighted gene coexpression network analysis, and the other three gene sets were obtained from public databases. Subsequently, we further explored the clinical value and immunoregulation of the hub gene of intersection. The relevant pathways related to hub gene expression were investigated by gene set enrichment analysis. Finally, the interaction of active compounds and target genes was validated by molecular docking. Key Findings. Thirteen active compounds and 90 target genes of Yinchen were included. After constructing the network among Yinchen, target genes, and HCC, BIRC5 was identified as the hub gene. Significant difference was found between the high-expressed group and the low-expressed group in survival and stage. Different immune subtypes also presented significant difference in BIRC5 expression. Moreover, NK cell and T cell (CD4+ effector memory and CD4+ memory resting) were negatively correlated with BIRC5 expression, while CTLA4 and LAG3 were positively correlated. The results of molecular docking further validated a good binding activity of quercetin-BIRC5 interaction. Significance. In summary, our research identified for the first time a novel underlying association among herbal medicine Yinchen, BIRC5, immunotherapy, and HCC. We speculated that Yinchen may target the immune checkpoints (CTLA4 and LAG3) and activate the immune cells by suppressing BIRC5. Hindawi 2020-12-29 /pmc/articles/PMC7785361/ /pubmed/33457419 http://dx.doi.org/10.1155/2020/8886914 Text en Copyright © 2020 Zhuomao Mo et al. https://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Mo, Zhuomao
Cao, Zhirui
Yu, Ling
Wang, Yongdan
Li, Pan
Lin, Youwu
Zhang, Shijun
An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma
title An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma
title_full An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma
title_fullStr An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma
title_full_unstemmed An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma
title_short An Integrative Analysis Reveals the Potential Mechanism between Herbal Medicine Yinchen and Immunoregulation in Hepatocellular Carcinoma
title_sort integrative analysis reveals the potential mechanism between herbal medicine yinchen and immunoregulation in hepatocellular carcinoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7785361/
https://www.ncbi.nlm.nih.gov/pubmed/33457419
http://dx.doi.org/10.1155/2020/8886914
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