肝癌ceRNA调控网络的分析研究  

comprehensive analysis of competing endogenous RNA network in Hepatocellular carcinoma

作　　者：张乙凡 潘耀振 陈玲 喻超 孙诚谊 ZHANG Yifan;PAN Yaozhen;CHEN Ling;YU Chao;SUN Chengyi

机构地区：[1]贵州医科大学附属医院肝胆外科,贵阳市550001 [2]贵州医科大学肝胆胰脾重点实验室,贵州医科大学,贵州省550025

出　　处：《中国研究型医院》2018年第3期25-32,共8页Chinese Research Hospitals

基　　金：贵州省高层次创新人才培养计划“十”层次人才,黔科合平台人才[2016]5647;贵州省孙诚谊“肝胆胰脾疾病诊治”导师工作室,黔教研合GZs[2016]09;贵州省肝胆外科临床医学研究中心,黔科合平台人才[2017]5404

摘　　要：目的:通过对TCGA数据库中肝癌和癌旁组织lnc RNA、mi RNA和m RNA进行差异表达分析,研究lnc RNA、mi RNA和m RNA对肝癌发生发展的影响。方法:用得到差异表达的lnc RNA、mi RNA和m RNA构建肝癌ce RNA调控网,明确肝癌中lnc RNA、mi RNA和m RNA之间相互作用的关系及其对肝癌发生发展的影响;为了进一步明确ce RNA调控网对肝癌疾病的作用,对ce RNA调控网中的m RNA进行GO注释分析、KEGG通路分析和蛋白互作分析。结果:发现调控网中的m RNA在肿瘤Mi RNAs、细胞周期、膀胱癌、黑色素瘤、小细胞肺癌、胰腺癌、前列腺癌、结肠癌、P53信号通路、PI3K-Akt信号通路、TGF-β信号通路等18个KEGG信号通路中明显富集(校正后的P<0.01),通过对肝癌ce RNA调控网中的lnc RNA、mi RNA和m RNA进行Kaplan-Meier曲线分析,筛选与肝癌预后有明显相关性的lnc RNA、mi RNA和m RNA。结论:lnc RNA LOC107985899影响mi RNA-137的表达,从而调控m RNA MITF的表达;lnc RNA C2orf48、C10orf91、LINC00114影响mi RNA-204的表达,从而调控m RNA ITPR1、BCL2、AP1S2、TGFBR2、SLC43A1、PRLR、ZCCHC24、ANGPTL2、CHRDL1的表达;lnc RNA LOC107985899影响mi RNA-222的表达,从而调控m RNA ESR1、TIMP3、ZEB2、GALNT3的表达。Objective： The differential expression analysis of lncRNAs, miRNAs and mRNAs in hepatocellular carcinoma and adjacent tissues in the TCGA database was performed to investigate the effects of lnc RNA, mi RNA and m RNA on the occurrence and development of hepatocellular carcinoma. Methods： In order to clarify the relationship between lncRNAs, miRNAs and mRNAs in liver cancer and their effects on the development of liver cancer, we used differential expressions of the lnc RNA, mi RNA and m RNA to construct liver cancer ce RNA regulatory networks. To further clarify the role of the ce RNA regulatory network in liver cancer disease, we performed GO annotated analysis, KEGG pathway analysis, and protein interaction analysis on the m RNA of the ce RNA regulatory network. Results： The results showed that the mRNAs in the regulatory network was significantly enriched in 18 KEGG signaling pathways such as tumor MiRNAs, cell cycle, bladder cancer, melanoma, small cell lung cancer, pancreatic cancer, prostate cancer, colon cancer, P53 signaling pathway, PI3 K-Akt signaling pathway and TGF-β signaling pathway（P〈0.01 after calibration）. Kaplan-Meier curve analysis of lncRNAs, miRNAs and mRNAs in hepatoma ce RNA regulatory networks was performed to screen lncRNAs, miRNAs and mRNAs that are significantly associated with the prognosis of liver cancer. Conclusion： lnc RNA LOC107985899 affects the expression of mi RNA-137 and thus regulates the m RNA expression of MITF; lncRNAs C2 orf48, C10 orf91 and LINC00114 influences the expression of mi RNA-204, which regulates m RNA expression of ITPR1, BCL2, AP1 S2, TGFBR2, SLC43 A1, PRLR, ZCCHC24, ANGPTL2 and CHRDL1; lnc RNA LOC107985899 affects the expression of mi RNA-222, which regulates the expression of m RNA ESR1, TIMP3, ZEB2 and GALNT3.

关 键 词：肝癌 长链非编码RNA MICRORNA TCGA 

分 类 号：R735.7[医药卫生—肿瘤]