基于癌症基因组图谱数据库的结直肠癌竞争性内源RNA网络的构建与分析
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摘要
目的探究基于癌症基因组图谱(the cancer genome atlas,TCGA)数据库的结直肠癌竞争性内源RNA(competing endogenous RNA,ceRNA)网络的构建,并分析其与结直肠癌预后相关性。方法从TCGA数据库中下载结直肠腺癌组织样本基因表达谱数据,根据生物信息学方法处理原始数据,利用TCGA数据库筛选发现差异表达的长链非编码RNA(long non-coding RNA,lncRNA)、微小RNA(microRNA,miRNA)、信使RNA(messenger RNA,mRNA),通过对差异表达的lncRNA和差异表达的miRNA的比对以及对差异miRNA靶基因的预测,建立三者联系,构建ceRNA网络。结果共鉴定出1 041个差异表达的lncRNA、278个差异表达的miRNA、4 258个差异表达的mRNA;构建了由123个lncRNA、46个miRNA和73个mRNA组成的ceRNA网络;发现有6个lncRNA、7个miRNA、9个mRNA与结直肠癌的预后相关。功能富集结果显示,mRNA主要参与调节蛋白酶活性、蛋白裂解、化学物质传递、细胞周期等功能。结论构建ceRNA网络为研究结直肠癌的发生、发展的调控机制提供了借鉴,与预后相关的lncRNA、miRNA、mRNA可能未来为结直肠癌提供分子诊断。
Objective To explore the construction and analysis of competitive endogenous RNA( ceRNA) network for colorectal cancer based on the cancer genome atlas( TCGA) database and to analyze the prognostic association with colorectal cancer.Methods Firstly,the expression profile data of colorectal adenocarcinoma tissue were searched and downloaded from TCGA database.The raw data were processed by the principles of bioinformatics. Differentially expressed long non-coding RNA( lncRNA) lncRNAs,microRNA( miRNA) and messenger RNA( mRNA) were screened and found by using TCGA database. Through the comparison of differential lncRNAs and differential miRNAs and the prediction of differential miRNA target genes,the relationship between the 3 was established and a ceRNA network was thus constructed. Results A total of 1 041 differentially expressed lncRNAs,279 differentially expressed miRNAs and 4 258 differentially expressed mRNAs were identified. A ceRNA network consisting of 123 lncRNAs,46 miRNAs and 73 mRNAs was constructed successfully. A total of 6 lncRNAs,7 miRNAs and 9 mRNAs were associated with the prognosis of colorectal cancer. Functional enrichment results showed that mRNAs were mainly involved in the regulation of protease activity,protein cleavage,chemical transport,cell cycle and other functions. Conclusion The construction of ceRNA network could provide evidence for the study of the mechanism involved in the regulation of the occurrence and development of colorectal cancer,and possibly provide molecular diagnosis and prognostic markers for colorectal cancer in future medical care.
Objective To explore the construction and analysis of competitive endogenous RNA( ceRNA) network for colorectal cancer based on the cancer genome atlas( TCGA) database and to analyze the prognostic association with colorectal cancer.Methods Firstly,the expression profile data of colorectal adenocarcinoma tissue were searched and downloaded from TCGA database.The raw data were processed by the principles of bioinformatics. Differentially expressed long non-coding RNA( lncRNA) lncRNAs,microRNA( miRNA) and messenger RNA( mRNA) were screened and found by using TCGA database. Through the comparison of differential lncRNAs and differential miRNAs and the prediction of differential miRNA target genes,the relationship between the 3 was established and a ceRNA network was thus constructed. Results A total of 1 041 differentially expressed lncRNAs,279 differentially expressed miRNAs and 4 258 differentially expressed mRNAs were identified. A ceRNA network consisting of 123 lncRNAs,46 miRNAs and 73 mRNAs was constructed successfully. A total of 6 lncRNAs,7 miRNAs and 9 mRNAs were associated with the prognosis of colorectal cancer. Functional enrichment results showed that mRNAs were mainly involved in the regulation of protease activity,protein cleavage,chemical transport,cell cycle and other functions. Conclusion The construction of ceRNA network could provide evidence for the study of the mechanism involved in the regulation of the occurrence and development of colorectal cancer,and possibly provide molecular diagnosis and prognostic markers for colorectal cancer in future medical care.
引文
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[2]Shah R,Jones E,Vidart V,et al.Biomarkers for early detection of colorectal cancer and polyps:systematic review[J].Cancer Epidemiol Biomark&Prev,2014,23(9):1712-1728.DOI:10.1158/1055-9965.EPI-14-0412.
[3]Zhang A,Sun H,Yan G,et al.Metabolomics in diagnosis and biomarker discovery of colorectal cancer[J].Cancer Lett,2014,345(1):17-20.DOI:10.1016/j.canlet.2013.11.011.
[4]Clancy C,Joyce MR,Kerin MJ.The use of circulating microRNAs as diagnostic biomarkers in colorectal cancer[J].Cancer Biomark,2015,15(2):103-113.DOI:10.3233/CBM-140456.
[5]Tay Y,Rinn J,Pandolfi PP.The multilayered complexity of ceRNA crosstalk and competition[J].Nature,2014,505(7483):344-352.DOI:10.1038/nature12986.
[6]姚宏伟,舒畅,胡松年,等.从精准医学看结直肠癌诊断与治疗的未来[J].中华胃肠外科杂志,2016,19(1):7-12.DOI:10.3760/cma.j.issn.1671-0274.2016.01.002.
[7]Huang W,Tian Y,Dong S,et al.The long non-coding RNA SNHG3 functions as a competing endogenous RNA to promote malignant development of colorectal cancer[J].Oncol Rep,2017,38(3):1402-1410.DOI:10.3892/or.2017.5837.
[8]Chen X,Chen Z,Yu S,et al.Long noncoding RNA LINC01234functions as a competing endogenous RNA to regulate CBFB expression by sponging miR-204-5p in gastric cancer[J].Clin Cancer Res,2018,24(8):2002-2014.DOI:10.1158/1078-0432.CCR-17-2376.
[9]Xie CR,Wang F,Zhang S,et al.Long noncoding RNA HCAL facilitates the growth and metastasis of hepatocellular carcinoma by acting as a ceRNA of LAPTM4B[J].Mol Ther Nucleic Acids,2017,9:440-451.DOI:10.1016/j.omtn.2017.10.018.
[10]Liu Y,Du Y,Hu X,et al.Up-regulation of ceRNA TINCR by SP1 contributes to tumorigenesis in breast cancer[J].BMC Cancer,2018,18(1):367.DOI:10.1186/s12885-018-4255-3.
[11]Liu T,Chi H,Chen J,et al.Curcumin suppresses proliferation and in vitro invasion of human prostate cancer stem cells by ceRNA effect of miR-145 and lncRNA-ROR[J].Gene,2017,631:29-38.DOI:10.1016/j.gene.2017.08.008.
[12]Luan W,Li L,Shi Y,et al.Long non-coding RNA MALAT1 acts as a competing endogenous RNA to promote malignant melanoma growth and metastasis by sponging miR-22[J].Oncotarget,2016,7(39):63901-63912.DOI:10.18632/oncotarget.11564.
[13]Yang W,Ning N,Jin X.The lncRNA H19 promotes cell proliferation by competitively binding to miR-200a and derepressingβ-Catenin expression in colorectal cancer[J].Biomed Res Int,2017,2017:2767484.DOI:10.1155/2017/2767484.
[14]Xu J,Zhang R,Zhao J.The novel long noncoding RNA TUSC7 inhibits proliferation by sponging MiR-211 in colorectal cancer[J].Cell Physiol Biochem,2017,41(2):635-644.DOI:10.1159/000457938.
[15]Huang J,Mo YY.Abstract 3537:Suppression of miR-145 by long noncoding RNA RoR in colon cancer[J].Cancer Research,2014,74(19 Supplement):3537-3537.DOI:10.1158/1538-7445.
[16]Jin J,Chu Z,Ma P,et al.Long non-coding RNA SPRY4-IT1 promotes proliferation and invasion by acting as a ceRNA of miR-101-3p in colorectal cancer cells[J].Tumour Biol,2017,39(7):1010428317716250.DOI:10.1177/1010428317716250.