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Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology

PURPOSE: Aimed to identify the anti-uterine corpus endometrial carcinoma (UCEC) function and characterize the mechanism of quercetin in the treatment of patients infected with COVID-19 via integrated in silico analysis. METHODS: The Cancer Genome Atlas and Genotype Tissue Expression databases were a...

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Autores principales: Li, Kehan, Liu, Hejing, Lin, Yibin, Gu, Liang, Xiang, Xinli, Zhu, Xueqiong
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031047/
https://www.ncbi.nlm.nih.gov/pubmed/36969077
http://dx.doi.org/10.3389/fonc.2023.1151434
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author Li, Kehan
Liu, Hejing
Lin, Yibin
Gu, Liang
Xiang, Xinli
Zhu, Xueqiong
author_facet Li, Kehan
Liu, Hejing
Lin, Yibin
Gu, Liang
Xiang, Xinli
Zhu, Xueqiong
author_sort Li, Kehan
collection PubMed
description PURPOSE: Aimed to identify the anti-uterine corpus endometrial carcinoma (UCEC) function and characterize the mechanism of quercetin in the treatment of patients infected with COVID-19 via integrated in silico analysis. METHODS: The Cancer Genome Atlas and Genotype Tissue Expression databases were applied to obtain differentially expressed genes of UCEC and non-tumor tissue. Several in silico methods such as network pharmacology, functional enrichment analysis, Cox regression analyses, somatic mutation analysis, immune infiltration and molecular docking were used to investigate and analysis the biological targets, functions and mechanisms of anti-UCEC/COVID-19 of quercetin. Multiple methods such as CCK8 assay, Transwell assay and western blotting were performed to test proliferation, migration, and protein level of UCEC (HEC-1 and Ishikawa) cells. RESULTS: Functional analysis disclosed that quercetin against UCEC/COVID-19 mainly by ‘biological regulation’, ‘response to stimulus’, and ‘regulation of cellular process’. Then, regression analyses indicated that 9 prognostic genes (including ANPEP, OAS1, SCGB1A1, HLA‐A, NPPB, FGB, CCL2, TLR4, and SERPINE1) might play important roles in quercetin for treating UCEC/COVID-19. Molecular docking analysis revealed that the protein products of 9 prognostic genes were the important anti-UCEC/COVID-19 biological targets of quercetin. Meanwhile, the proliferation and migration of UCEC cells were inhibited by quercetin. Moreover, after treatment with quercetin, the protein level of ubiquitination-related gene ISG15 was decreased in UCEC cells in vitro. CONCLUSIONS: Taken together, this study provides new treatment option for UCEC patients infected with COVID-19. Quercetin may work by reducing the expression of ISG15 and participating in ubiquitination-related pathways.
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spelling pubmed-100310472023-03-23 Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology Li, Kehan Liu, Hejing Lin, Yibin Gu, Liang Xiang, Xinli Zhu, Xueqiong Front Oncol Oncology PURPOSE: Aimed to identify the anti-uterine corpus endometrial carcinoma (UCEC) function and characterize the mechanism of quercetin in the treatment of patients infected with COVID-19 via integrated in silico analysis. METHODS: The Cancer Genome Atlas and Genotype Tissue Expression databases were applied to obtain differentially expressed genes of UCEC and non-tumor tissue. Several in silico methods such as network pharmacology, functional enrichment analysis, Cox regression analyses, somatic mutation analysis, immune infiltration and molecular docking were used to investigate and analysis the biological targets, functions and mechanisms of anti-UCEC/COVID-19 of quercetin. Multiple methods such as CCK8 assay, Transwell assay and western blotting were performed to test proliferation, migration, and protein level of UCEC (HEC-1 and Ishikawa) cells. RESULTS: Functional analysis disclosed that quercetin against UCEC/COVID-19 mainly by ‘biological regulation’, ‘response to stimulus’, and ‘regulation of cellular process’. Then, regression analyses indicated that 9 prognostic genes (including ANPEP, OAS1, SCGB1A1, HLA‐A, NPPB, FGB, CCL2, TLR4, and SERPINE1) might play important roles in quercetin for treating UCEC/COVID-19. Molecular docking analysis revealed that the protein products of 9 prognostic genes were the important anti-UCEC/COVID-19 biological targets of quercetin. Meanwhile, the proliferation and migration of UCEC cells were inhibited by quercetin. Moreover, after treatment with quercetin, the protein level of ubiquitination-related gene ISG15 was decreased in UCEC cells in vitro. CONCLUSIONS: Taken together, this study provides new treatment option for UCEC patients infected with COVID-19. Quercetin may work by reducing the expression of ISG15 and participating in ubiquitination-related pathways. Frontiers Media S.A. 2023-03-08 /pmc/articles/PMC10031047/ /pubmed/36969077 http://dx.doi.org/10.3389/fonc.2023.1151434 Text en Copyright © 2023 Li, Liu, Lin, Gu, Xiang and Zhu https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Oncology
Li, Kehan
Liu, Hejing
Lin, Yibin
Gu, Liang
Xiang, Xinli
Zhu, Xueqiong
Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology
title Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology
title_full Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology
title_fullStr Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology
title_full_unstemmed Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology
title_short Discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with COVID-19 through network pharmacology
title_sort discovery of therapeutic targets of quercetin for endometrial carcinoma patients infected with covid-19 through network pharmacology
topic Oncology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10031047/
https://www.ncbi.nlm.nih.gov/pubmed/36969077
http://dx.doi.org/10.3389/fonc.2023.1151434
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