引用本文:李冰滢,刘 畅,李 枫,张庆梅,罗 彬,葛盈盈,农蔚霞,陈 芳,肖绍文,谢小薰.肾嫌色细胞癌ceRNA调控网络的构建与分析[J].中国临床新医学,2021,14(6):600-605.
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肾嫌色细胞癌ceRNA调控网络的构建与分析
李冰滢,刘 畅,李 枫,张庆梅,罗 彬,葛盈盈,农蔚霞,陈 芳,肖绍文,谢小薰
530021 南宁,广西医科大学组织学与胚胎学教研室(李冰滢,李 枫,张庆梅,罗 彬,葛盈盈,农蔚霞,陈 芳,谢小薰),基础医学中心实验室(张庆梅,罗 彬,葛盈盈,农蔚霞,陈 芳,谢小薰);530021 南宁,广西医科大学第一附属医院神经外科(刘 畅,肖绍文)
摘要:
[摘要] 目的 构建肾嫌色细胞癌(CRCC)的内源竞争性RNA(ceRNA)调控网络,筛选出与CRCC预后相关的信使RNA(mRNA)、长非编码RNA(lncRNA)和微小RNA(miRNA),为CRCC的诊断和预后提供理论依据。方法 提取TCGA数据库中CRCC样本(65例)和正常肾样本(24例)的转录组数据,以错误发现率(FDR)<0.05,差异倍数的对数绝对值(log2|FC|)>2为条件筛选差异表达(DE)的lncRNA、miRNA和mRNA,据此构建ceRNA调控网络。应用Kaplan-Meier法探讨与CRCC患者预后相关的因子,据此进一步构建蛋白-蛋白互作(PPI)网络,并进行GO与KEGG富集分析。结果 共筛选出3 679个DElncRNA,297个DEmiRNA和5 914个DEmRNA。mRNA下调的ceRNA网络包含DEmiRNA 95个、DEmRNA 268个、DElncRNA 737个;mRNA上调的ceRNA网络包含DEmiRNA 85个、DEmRNA 234个、DElncRNA 924个。Kaplan-Meier分析筛选出3个DEmRNA(DEPDC1、SLC7A11和E2F7)和1个DEmiRNA(miR-26b-5p)与CRCC预后存在关联(P<0.05)。以DEPDC1、SLC7A11和E2F7构建的PPI网络中共含有8个mRNA(TOP2A、DEPDC1、SLC3A2、E2F8、SLC7A11、E2F1、TP53和E2F7)参与蛋白互作,GO和KEGG富集分析显示,这些互作蛋白功能主要富集于DNA损伤反应、p53介导的细胞组织与启动子特异结合、铁死亡,以及肿癌疾病相关信号通路。结论 该研究通过构建CRCC的ceRNA调控网络筛选出与其预后相关的关键RNAs,为CRCC的诊断和治疗提供了理论依据。
关键词:  肾嫌色细胞癌  内源竞争性RNA调控网络  信使RNA  长非编码RNA  微小RNA
DOI:10.3969/j.issn.1674-3806.2021.06.16
分类号:R 737.11
基金项目:广西区域性高发肿瘤早期防治研究教育部重点实验室课题(编号:GKEZZ2019-08,GKE-ZZ202006)
Construction and analysis of competing endogenous RNAs regulatory network in chromophobe renal cell carcinoma
LI Bing-ying, LIU Chang, LI Feng, et al.
Department of Histology and Embryology, Guangxi Medical University, Nanning 530021, China
Abstract:
[Abstract] Objective To construct a competing endogenous RNAs(ceRNA) regulatory network for chromophobe renal cell carcinoma(CRCC), and to screen out messenger RNA(mRNA), long non-coding RNA(lncRNA) and micro RNA(miRNA) related to the prognosis of CRCC, so as to provide a theoretical basis for the diagnosis and prognosis of CRCC. Methods The transcriptome data of CRCC samples(65 cases) and normal kidney specimens(24 cases) were extracted from the Cancer Genome Atlas(TCGA) database, and the differentially expressed(DE) lncRNA, miRNA and mRNA were screened under the condition of false discovery rate(FDR)<0.05 and absolute logarithm of fold change(log2|FC|)>2. Based on these, the ceRNA regulatory network was constructed. The Kaplan-Meier method was used to explore the factors related to the prognosis of CRCC patients, and based on this, the protein-protein interaction(PPI) network was further constructed, and Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis was performed. Results A total of 3 679 DElncRNA, 297 DEmiRNA and 5 914 DEmRNA were screened.The down-regulated mRNA ceRNA network contained 95 DEmiRNA, 268 DEmRNA, and 737 DElncRNA; the up-regulated mRNA ceRNA network contained 85 DEmiRNA, 234 DEmRNA, and 924 DElncRNA. Kaplan-Meier analysis screened out 3 DEmRNAs(DEPDC1, SLC7A11 and E2F7) and 1 DEmiRNA(miR-26b-5p), which were associated with the prognosis of CRCC(P<0.05). The PPI network constructed with DEPDC1, SLC7A11 and E2F7 contained a total of 8 mRNAs(TOP2A, DEPDC1, SLC3A2, E2F8, SLC7A11, E2F1, TP53 and E2F7) that participated in protein interactions. The enrichment analysis of GO and KEGG showed that these interaction proteins function mainly enriched in DNA damage response, p53-mediated cell tissue and promoter specific binding, iron death, and tumor-associated signal pathways. Conclusion In this study, the key RNAs related to CRCC prognosis are screened out by constructing the ceRNA regulatory network of CRCC, which provides a theoretical basis for the diagnosis and treatment of CRCC.
Key words:  Chromophobe renal cell carcinoma(CRCC)  Competing endogenous RNAs(ceRNA) regulatory network  Messenger RNA(mRNA)  Long non-coding RNA(lncRNA)  Micro RNA(miRNA)