Research Paper Volume 16, Issue 1 pp 518—537
New perspectives on the potential of tetrandrine in the treatment of non-small cell lung cancer: bioinformatics, Mendelian randomization study and experimental investigation
- 1 Department of Oncology, The First Affiliated Hospital of Jinan University, Jinan University, Guangzhou, China
- 2 Department of Infectious Diseases, Affiliated Hospital of Zunyi Medical University, Zunyi, China
- 3 Department of Neurology and Stroke Centre, The First Affiliated Hospital of Jinan University, Guangzhou, China
Received: September 4, 2023 Accepted: November 16, 2023 Published: January 4, 2024
https://doi.org/10.18632/aging.205384How to Cite
Copyright: © 2024 Luo et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Abstract
Background: Although there are numerous treatment methods for NSCLC, long-term survival remains a challenge for patients. The objective of this study is to investigate the role and causal relationship between the target of tetrandrine and non-small cell lung cancer (NSCLC) through transcriptome and single-cell sequencing data, summary-data-based Mendelian Randomization (SMR) and basic experiments. The aim is to provide a new perspective for the treatment of NSCLC.
Methods: We obtained the drug target gene of tetrandrine through the drug database, and then used the GSE19188 data set to obtain the NSCLC pathogenic gene, established a drug-disease gene interaction network, screened out the hub drug-disease gene, and performed bioinformatics and tumor cell immune infiltration analysis. Single-cell sequencing data (GSE148071) to determine gene location, SMR to clarify causality and drug experiment verification.
Results: 10 drug-disease genes were obtained from 213 drug targets and 529 disease genes. DO/GO/KEGG analysis showed that the above genes were all related to the progression and invasion of NSCLC. Four drug-disease genes were identified from a drug-disease PPI network. These four genes were highly expressed in tumors and positively correlated with plasma cells, T cells, and macrophages. Subsequent single-cell sequencing data confirmed that these four genes were distributed in epithelial cells, and SMR analysis revealed the causal relationship between CCNA2 and CCNB1 and the development of NSCLC. The final molecular docking and drug experiments showed that CCNA2 and CCNB1 are key targets for tetrandrine in the treatment of NSCLC.
Abbreviations
BP: biological process; CHM: Chinese herbal medicine; CNB: Cinobufacin; CTD: Comparative Toxicogenomics Database; CC: cellular component; DO: Disease Ontology; GO: Gene Ontology; ICAM-1: intercellular adhesion molecule-1; KEGG: Kyoto Encyclopedia of Genes and Genomes; MF: molecular function; NSCLC: Non-small cell lung cancer; PPI: protein-protein interaction; PCA: Principal Component Analysis; QC: quality control; ROC: receiver operating characteristic; TB: theabrownin; UMAP: Uniform Manifold Approximation and Projection; VEGF: vascular endothelial growth factor; YYJD: Yiqi Yangyin Jiedu Decoction.