Screening of Hub Genes and Therapeutic Drugs in Cervical Cancer Using Integrated Bioinformatics Analysis.

Abstract

Objective: Cervical cancer (CC) is one of the most common female malignancies globally. The current study aimed to identify novel hub genes associated with traditional Chinese herbs and investigate their underlying mechanisms using bioinformatics analysis combined with experimental verification. Methods: Expression profiling of 22 samples was obtained from the GEO database. Differential expression analysis was performed using the limma package in R. The Chinese herbal formulas related to the treatment of cervical cancer were searched in the TCMIP database using the keyword "cervical cancer". disease targets associated with cervical cancer were retrieved based on six databases, including the DisGeNet, Genecards, CTD, OMIM, GEO, and TTD databases. The database STRING and Cytoscape were utilized to determine candidate hub genes. The hub genes were further investigated using UALCAN, Kaplan‒Meier-plotter databases, Human Protein Atlas, and the AutoDock Vina software. The results of network pharmacology analysis were verified by in vitro experiments. Results: By intersecting the disease targets with the drug targets, we obtained 49 possible therapeutic targets for cervical cancer. Afterward, we analyzed 49 therapeutic targets using the STRING database and the cytoHubba plugin and eventually obtained six hub genes, MYC, HIF1A, TP53, STAT3, CCND1, and AKT1. The final hub genes were indicated to have significant prognostic relevance in cervical cancer. In addition, the six hub genes were molecularly docked with traditional Chinese medicine for cancer, including quercetin, licochalcone a, nobiletin, naringin, and kaempferol. The results also showed that traditional Chinese medicine could decrease the mRNA and protein expressions, suggesting that quercetin, licochalcone a, nobiletin, naringin, and kaempferol can treat CC by inducing cell apoptosis. Conclusions: We identify six genes that can be therapeutic targets for cervical cancer, confirm that quercetin, licochalcone a, nobiletin, naringin, and kaempferol exert therapeutic effects on cervical cancer by regulating apoptosis pathways through in vitro experiments, and provide insights into the molecular mechanisms of the impact of traditional Chinese medicine in cancer treatment.