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硫利达嗪抗宫颈癌的潜在作用机制
作者姓名:谢芹  赵春阳  张葆溯  赵洪波
作者单位:昆明医科大学生物医学工程研究院暨云南省干细胞和再生医学重点实验室,云南 昆明 650500
基金项目:云南省科技厅-昆明医科大学应用基础研究联合专项基金资助项目(202101AY070001-075);云南省教育厅科学研究基金资助项目(2021J0226)
摘    要:目的 运用生物信息学分析,探讨硫利达嗪抗宫颈癌的潜在作用机制.方法 通过PharmMapper工具预测能够与硫利达嗪相互作用的靶基因,然后使用STRING在线工具对靶基因进行通路和组织表达富集分析.使用GeneCards和DisGeNET数据库筛选宫颈癌相关基因,与硫利达嗪的靶基因取交集,得到硫利达嗪可能作用于宫颈癌的...

关 键 词:硫利达嗪  宫颈癌  靶点  作用机制
收稿时间:2022-02-01

Potential Mechanism of Thioridazine in Anti-cervical Cancer
Affiliation:Institute of Biomedical Engineering & Yunnan Key Laboratory of Stem Cell and Regenerative Medicine,Kunming Medical University,Kunming Yunnan 650500,China
Abstract:  Objective  To explore the potential mechanism of thioridazine in the treatment of cervical cancer by bioinformatics analysis.   Methods  The target genes that can interact with thioridazine was predicted by PharmMapper, and then conducted pathway and tissue expression enrichment analysis by STRING online tool. The cervical cancer related genes were screened through GeneCards and DisGeNET databases, and cross the target genes of thioridazine to obtain the interaction genes that thioridazine may act on cervical cancer. The protein-protein interaction(PPI) network was constructed using STRING, and the core targets were speculated and evaluated their importance.The GO and KEGG enrichment analysis were conducted using clusterProfiler package.   Results  A total of 47 target genes were predicted by PharmMapper, which were enriched in tumor-related pathways and cervical cancer cells. Intersection with 669 cervical cancer genes, 21 common genes were obtained, of which 10 key genes were EGFR, PPARG, AR, NOS3, ALB, ESR1, MAPK1, MAPK14, ANXA5 and MAPK8. These key genes were important in the cervical cancer PPI network. The biological processes involved in interactive genes mainly include positive regulation of anion transport, peptidyl-serine phosphorylation, steroid metabolic process, blood coagulation, and cellular response to chemical stress. Enriched KEGG pathways include pathways in cancer, relaxin signaling pathway, endocrine resistance, proteoglycans in cancer, cellular senescence, GnRH signaling pathway, and VEGF signaling pathway.   Conclusion  Thioridazine has potential anti-tumor effects and may play a role in the treatment of cervical cancer through multiple targets and multiple signaling pathways.
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