Construction and comprehensive analysis of a ceRNA network to reveal potential prognostic biomarkers for hepatocellular carcinoma

Junyu Long,Li He,Xiaobo Yang,Xu Yang,Yi Bai,Dongxu Wang,Yongchang Zheng,Jianzhen Lin,Haitao Zhao

doi:10.1186/s12935-019-0817-y

Abstract

BackgroundLong noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression; therefore, lncRNAs are considered a major part of the competitive endogenous RNA (ceRNA) network and have attracted growing attention. The present study explored the regulatory mechanisms and functional roles of lncRNAs as ceRNAs in hepatocellular carcinoma (HCC) and their potential impact on HCC patient prognosis.MethodsIn this study, we systematically studied the expression profiles and prognostic value of lncRNA, miRNA, and mRNA from a total of 838 HCC patients from five HCC cohorts (TCGA, GSE54236, GSE76427, GSE64041 and GSE14520). The TCGA, GSE54236 and GSE76427 HCC cohorts were utilized to establish a prognosis-related network of dysregulated ceRNAs by bioinformatics methods. The GSE64041 and GSE14520 HCC cohorts were utilized to verify the expression of candidate genes.ResultsIn total, 721 lncRNAs, 73 miRNAs, and 1563 mRNAs were aberrantly expressed in HCC samples. A ceRNA network including 26 lncRNAs, four miRNAs, and six mRNAs specific to HCC was established. The survival analysis showed that four lncRNAs (MYCNOS, DLX6-AS1, LINC00221, and CRNDE) and two mRNAs (CCNB1 and SHCBP1) were prognostic biomarkers for patients with HCC in both the TCGA and GEO databases.ConclusionThe proposed ceRNA network may help elucidate the regulatory mechanism by which lncRNAs function as ceRNAs and contribute to the pathogenesis of HCC. Importantly, the candidate lncRNAs, miRNAs, and mRNAs involved in the ceRNA network can be further evaluated as potential therapeutic targets and prognostic biomarkers for HCC.

Highlights

Long noncoding RNAs can act as microRNA sponges to regulate protein-coding gene expression; long noncoding RNA (lncRNA) are considered a major part of the competitive endogenous RNA network and have attracted growing attention
The survival analysis showed that four lncRNAs (MYCNOS, DLX6-AS1, LINC00221, and CRNDE) and two mRNAs (CCNB1 and SHCBP1) were prognostic biomarkers for patients with hepatocellular carcinoma (HCC) in both the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases
differentially expressed gene (DEG) in HCC Using a cut-off threshold of |log2 fold change (FC)| > 2 and an adjusted P-value < 0.01 for the 50 HCC tissues compared with the paired 50 nontumorous samples, we identified 641 DElncRNAs, 70 differentially expressed miRNA (DEmiRNA), and 1392 differentially expressed mRNA (DEmRNA)

Summary

Introduction

Long noncoding RNAs (lncRNAs) can act as microRNA (miRNA) sponges to regulate protein-coding gene expression; lncRNAs are considered a major part of the competitive endogenous RNA (ceRNA) network and have attracted growing attention. The present study explored the regulatory mechanisms and functional roles of lncRNAs as ceRNAs in hepatocellular carcinoma (HCC) and their potential impact on HCC patient prognosis. Hepatocellular carcinoma (HCC) is a severe cancer with an increasing incidence and is the fifth most prevalent cancer worldwide [1,2,3]. Viral infections, such as hepatitis B and hepatitis C, are usually associated with. Many researchers are working to reveal the different biological functions of lncRNAs in malignant tumors

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Conclusion