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基于综合生物信息学分析的宫颈癌关键基因及治疗药物筛选

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

作者信息

Talihati Ziruo, Abudurousuli Kayisaier, Hailati Sendaer, Han Mengyuan, Nuer Muhadaisi, Khan Nawaz, Maihemuti Nulibiya, Simayi Jimilihan, Zhang Weiyi, Zhou Wenting

机构信息

Department of Pharmacology, School of Pharmacy, Xinjiang Medical University, Xinjiang, China.

Xinjiang Key Laboratory of Natural Medicines Active Components and Drug Release Technology, Xinjiang, China.

出版信息

J Cancer. 2025 Jan 1;16(1):92-109. doi: 10.7150/jca.87027. eCollection 2025.

Abstract

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. 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 experiments. 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. 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 experiments, and provide insights into the molecular mechanisms of the impact of traditional Chinese medicine in cancer treatment.

摘要

宫颈癌(CC)是全球最常见的女性恶性肿瘤之一。本研究旨在通过生物信息学分析结合实验验证,鉴定与中药相关的新型核心基因,并探究其潜在机制。从基因表达综合数据库(GEO数据库)获取了22个样本的表达谱。使用R语言中的limma软件包进行差异表达分析。在中医综合数据库(TCMIP数据库)中,使用关键词“宫颈癌”搜索与宫颈癌治疗相关的中药方剂。基于包括疾病基因网络数据库(DisGeNet)、基因卡片数据库(Genecards)、比较毒理基因组学数据库(CTD)、在线孟德尔人类遗传数据库(OMIM)、基因表达综合数据库(GEO)和治疗靶点数据库(TTD)在内的六个数据库,检索与宫颈癌相关的疾病靶点。利用STRING数据库和Cytoscape软件确定候选核心基因。使用UALCAN数据库、Kaplan-Meier生存曲线分析数据库、人类蛋白质图谱数据库和AutoDock Vina软件对核心基因进行进一步研究。通过实验验证网络药理学分析的结果。通过将疾病靶点与药物靶点进行交叉分析,我们获得了49个可能的宫颈癌治疗靶点。随后,我们使用STRING数据库和cytoHubba插件对这49个治疗靶点进行分析,最终获得了六个核心基因,即MYC、缺氧诱导因子1α(HIF1A)、肿瘤蛋白p53(TP53)、信号转导和转录激活因子3(STAT3)、细胞周期蛋白D1(CCND1)和蛋白激酶B(AKT1)。结果表明,这些最终确定的核心基因在宫颈癌中具有显著的预后相关性。此外,将这六个核心基因与抗癌中药进行分子对接,这些中药包括槲皮素、甘草查尔酮A、川陈皮素、柚皮苷和山奈酚。结果还表明,这些中药可降低mRNA和蛋白表达,提示槲皮素、甘草查尔酮A、川陈皮素、柚皮苷和山奈酚可通过诱导细胞凋亡来治疗宫颈癌。我们鉴定出六个可作为宫颈癌治疗靶点的基因,通过实验证实槲皮素、甘草查尔酮A、川陈皮素、柚皮苷和山奈酚通过调节凋亡途径对宫颈癌发挥治疗作用,并为中药在癌症治疗中的作用分子机制提供了见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2c17/11660142/aae608f7192e/jcav16p0092g001.jpg

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