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

Fulai Zhao; Peng Zhao; Junli Chang; Xingyuan Sun; Xiaoping Ma; Binhao Shi; Mengchen Yin; Yongjun Wang; Yanping Yang

doi:10.3389/fgene.2023.1112671

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

Front Genet. 2023 Feb 7:14:1112671. doi: 10.3389/fgene.2023.1112671. eCollection 2023.

Authors

Fulai Zhao^{1

2}, Peng Zhao^{1

2}, Junli Chang^{1

2}, Xingyuan Sun^{1

2}, Xiaoping Ma^{1

2}, Binhao Shi^{1

2}, Mengchen Yin^{1

2}, Yongjun Wang^{1

2}, Yanping Yang^{1

2}

Affiliations

¹ Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
² Key Laboratory of Theory and Therapy of Muscles and Bones, Ministry of Education, Shanghai, China.

Abstract

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.

Keywords: Epithelial-Mesenchymal Transition; active ingredients in Chonglou; bioinformatics; drug targets; lung adenocarcinoma; network pharmacology.

Grants and funding

This work was supported by 1) National Key R&D Program of China (2018YFC1704300 and 2020YFE0201600); 2) National Nature Science Foundation (81973877, 82174408); 3) Shanghai Collaborative Innovation Center of Industrial Transformation of Hospital TCM Preparation.