Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes
Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been wi...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-02-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1112671/full |
| _version_ | 1828040116168294400 |
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| author | Fulai Zhao Fulai Zhao Peng Zhao Peng Zhao Junli Chang Junli Chang Xingyuan Sun Xingyuan Sun Xiaoping Ma Xiaoping Ma Binhao Shi Binhao Shi Mengchen Yin Mengchen Yin Yongjun Wang Yongjun Wang Yanping Yang Yanping Yang |
| author_facet | Fulai Zhao Fulai Zhao Peng Zhao Peng Zhao Junli Chang Junli Chang Xingyuan Sun Xingyuan Sun Xiaoping Ma Xiaoping Ma Binhao Shi Binhao Shi Mengchen Yin Mengchen Yin Yongjun Wang Yongjun Wang Yanping Yang Yanping Yang |
| author_sort | Fulai Zhao |
| collection | DOAJ |
| description | Lung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment. |
| first_indexed | 2024-04-10T16:52:34Z |
| format | Article |
| id | doaj.art-f110b58239b942e6bce9430220d60710 |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T16:52:34Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-f110b58239b942e6bce9430220d607102023-02-07T15:44:15ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-02-011410.3389/fgene.2023.11126711112671Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genesFulai Zhao0Fulai Zhao1Peng Zhao2Peng Zhao3Junli Chang4Junli Chang5Xingyuan Sun6Xingyuan Sun7Xiaoping Ma8Xiaoping Ma9Binhao Shi10Binhao Shi11Mengchen Yin12Mengchen Yin13Yongjun Wang14Yongjun Wang15Yanping Yang16Yanping Yang17Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLonghua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaKey Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, ChinaLung adenocarcinoma (LUAD) is the main histological type of lung cancer with an unfavorable survival rate. Metastasis is the leading LUAD-related death with Epithelial-Mesenchymal Transition (EMT) playing an essential role. The anticancer efficacies of the active ingredients in Chonglou have been widely reported in various cancers. However, the potential therapeutic targets of the Chonglou active ingredients in LUAD patients remain unknown. Here, the network pharmacology and bioinformatics were performed to analyze the associations of the clinical characteristics, immune infiltration factors and m6A-related genes with the EMT-related genes associated with LUAD (EMT-LUAD related genes), and the molecular docking, STRING, GO, and KEGG enrichment for the drug targets of Chonglou active ingredients associated with EMT (EMT-LUAD-Chonglou related genes). And, cell viability analysis and cell invasion and infiltration analysis were used to confirm the theoretical basis of this study. A total of 166 EMT-LUAD related genes were identified and a multivariate Cox proportional hazards regression model with a favorable predictive accuracy was constructed. Meanwhile, the immune cell infiltration, immune cell subsets, checkpoint inhibitors and the expression of m6A-related genes were significantly associated with the risk scores for EMT-LUAD related genes with independent significant prognostic value of all included LUAD patients. Furthermore, 12 EMT-LUAD-Chonglou related genes with five core drug targets were identified, which participated in LUAD development through extracellular matrix disassembly, collagen metabolic process, collagen catabolic process, extracellular matrix organization, extracellular structure organization and inflammatory response. Moreover, we found that the active ingredients of Chonglou could indeed inhibit the progression of lung adenocarcinoma cells. These results are oriented towards EMT-related genes to achieve a better understanding of the role of Chonglou and its targets in osteosarcoma development and metastasis, thus guiding future preclinical studies and facilitating clinical translation of LUAD treatment.https://www.frontiersin.org/articles/10.3389/fgene.2023.1112671/fulllung adenocarcinomaEpithelial-Mesenchymal Transitiondrug targetsactive ingredients in Chongloubioinformaticsnetwork pharmacology |
| spellingShingle | Fulai Zhao Fulai Zhao Peng Zhao Peng Zhao Junli Chang Junli Chang Xingyuan Sun Xingyuan Sun Xiaoping Ma Xiaoping Ma Binhao Shi Binhao Shi Mengchen Yin Mengchen Yin Yongjun Wang Yongjun Wang Yanping Yang Yanping Yang Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes Frontiers in Genetics lung adenocarcinoma Epithelial-Mesenchymal Transition drug targets active ingredients in Chonglou bioinformatics network pharmacology |
| title | Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes |
| title_full | Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes |
| title_fullStr | Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes |
| title_full_unstemmed | Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes |
| title_short | Identification and vitro verification of the potential drug targets of active ingredients of Chonglou in the treatment of lung adenocarcinoma based on EMT-related genes |
| title_sort | identification and vitro verification of the potential drug targets of active ingredients of chonglou in the treatment of lung adenocarcinoma based on emt related genes |
| topic | lung adenocarcinoma Epithelial-Mesenchymal Transition drug targets active ingredients in Chonglou bioinformatics network pharmacology |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1112671/full |
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