摘要
目的 探究卵巢癌铁死亡关键差异基因及其潜在作用机制。方法 基于Illumina测序平台对铁死亡诱导剂大鼠肉瘤基因选择性致死化合物3(RSL3)给药后的卵巢癌OVCAR8细胞株进行转录组测序。采用DESeq2算法筛选卵巢癌铁死亡差异基因,并采用基因本体(GO)、京都基因与基因组百科全书(KEGG)、基因集富集分析(GSEA)和蛋白互作网络(PPI)分析对差异基因富集的分子功能和信号通路进行综合分析。结果 转录组测序数据质控合格,平均比对率为(0.968±0.002)%。差异分析共筛选出1 834个铁死亡差异基因,其中包括805个上调基因和1 029个下调基因。GO和KEGG分析显示差异基因主要富集在细胞周期相关生物学功能以及铁死亡、内质网蛋白加工、p53信号通路、丙氨酸、天冬氨酸和谷氨酸代谢等信号通路。GSEA分析显示诱导卵巢癌细胞铁死亡激活了单加氧酶活性、铁离子集合等分子功能,过氧化物生物合成、花生四烯代谢和铁离子响应等生物学过程以及干扰素α、β信号、下调顺铂耐药、铁摄取和转运等信号通路。PPI分析确定了5个铁死亡关键差异基因,包括细胞周期蛋白依赖性激酶1(CDK1)、细胞周期蛋白A2(CCNA2)、细胞周期蛋白B1(CCNB1)、polo样激酶1(PLK1)、乳腺癌1号基因(BRCA1)。结论 基于转录组测序和生物信息学分析能有效识别卵巢癌铁死亡差异基因及其信号通路,为靶向铁死亡开发新的卵巢癌治疗策略提供了潜在的药物作用靶点。
Objective This study aims to explore key differential genes and potential mechanisms related to ferroptosis in ovarian cancer.Methods Transcriptome sequencing was conducted on the ovarian cancer cell line OVCAR8 after treatment with the ferroptosis inducer ras-selective lethal 3(RSL3),utilizing the Illumina sequencing platform.The DESeq2 algorithm was applied to identify differential genes associated with ferroptosis in ovarian cancer.A comprehensive analysis of molecular functions and signaling pathways enriched in these differential genes was carried out through Gene Ontology(GO),Kyoto Encyclopedia of Genes and Genomes(KEGG),Gene Set Enrichment Analysis(GSEA),and Protein-Protein Interaction(PPI) network analysis.Results The transcriptome sequencing data passed quality control,with a total alignment rate of(0.968±0.002) %.A total of 1 834 differential genes related to ferroptosis were identified,comprising 805 up-regulated genes and 1 029 down-regulated genes.GO and KEGG analyses revealed that differential genes were mainly enriched in biological functions related to the cell cycle,as well as signaling pathways involved in ferroptosis,protein processing in endoplasmic reticulum,p53 signaling pathway,alanine,aspartate,and glutamate metabolism,among others.GSEA analysis revealed activation of molecular functions such as monooxygenase activity and iron ion binding,biological processes including hydrogen peroxide biosynthetic precess,arachidonic acid metabolic process,and response to iron ion,as well as signaling pathways related to interferon alpha and beta signaling,downregulation of cisplatin resistance,iron uptake and transport.PPI analysis identified 5 key differential genes associated with ferroptosis,which included cyclin-dependent kinase 1(CDK1),cyclin A2(CCNA2),cyclin B1(CCNB1),polo-like kinase 1(PLK1) and breast cancer gene 1(BRCA1).Conclusion Transcrip tome sequencing and bioinformatics analysis can effectively identify differential genes and signaling pathways associated with ferroptosis in ovarian canc
作者
刘易陇
何霞
宋学武
童荣生
LIU Yi-long;HE Xia;SONG Xue-wu;TONG Rong-sheng(School of Medicine,University of Electronic Science and Technology of China,Chengdu 610054,Sichuan Province,China;Department of Pharmacy,The People's Hospital of Leshan,Leshan 614000,Sichuan Province,China;Personalized Drug Therapy Key Laboratory of Sichuan Provincial,Department of Pharmacy,Sichuan Academy of Medical Sciences&Sichuan Provincial People's Hospital/Affiliated Hospital of University of Electronic Science and Technology of China,Chengdu 610072,Sichuan Province,China)
出处
《中国临床药理学杂志》
CAS
CSCD
北大核心
2023年第24期3660-3663,共4页
The Chinese Journal of Clinical Pharmacology
基金
国家重点研发计划基金资助项目(2020YFC2005500)
国家自然科学基金面上资助项目(72174038)
四川省科技厅重点研发计划基金资助项目(2022YFS0272)
四川省医院协会青年药师科研专项基金资助项目(22008)
个体化药物治疗四川省重点实验室开放课题资助项目(2021ZD02)
四川省医学科学院·四川省人民医院科研基金资助项目(2020LY06)。
