Cancer Specific Long Noncoding RNAs Show Differential Expression Patterns and Competing Endogenous RNA Potential in Hepatocellular Carcinoma

Jian Zhang; Dahua Fan; Zhixiang Jian; George G Chen; Paul B S Lai

doi:10.1371/journal.pone.0141042

Cancer Specific Long Noncoding RNAs Show Differential Expression Patterns and Competing Endogenous RNA Potential in Hepatocellular Carcinoma

PLoS One. 2015 Oct 22;10(10):e0141042. doi: 10.1371/journal.pone.0141042. eCollection 2015.

Authors

Jian Zhang¹, Dahua Fan², Zhixiang Jian³, George G Chen⁴, Paul B S Lai⁴

Affiliations

¹ Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China; Division of Gastrointestinal Surgery & Gastric Cancer Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
² The First Affiliated Hospital of Shenzhen University, Shenzhen, Guangdong, China.
³ Department of General Surgery, Guangdong General Hospital, Guangdong Academy of Medical Sciences, Guangzhou, Guangdong, China.
⁴ Department of Surgery, The Chinese University of Hong Kong, Prince of Wales Hospital, Shatin, New Territories, Hong Kong SAR, China.

Abstract

Long noncoding RNAs (lncRNAs) regulate gene expression by acting with microRNAs (miRNAs). However, the roles of cancer specific lncRNA and its related competitive endogenous RNAs (ceRNA) network in hepatocellular cell carcinoma (HCC) are not fully understood. The lncRNA profiles in 372 HCC patients, including 372 tumor and 48 adjacent non-tumor liver tissues, from The Cancer Genome Atlas (TCGA) and NCBI GEO omnibus (GSE65485) were analyzed. Cancer specific lncRNAs (or HCC related lncRNAs) were identified and correlated with clinical features. Based on bioinformatics generated from miRcode, starBase, and miRTarBase, we constructed an lncRNA-miRNA-mRNA network (ceRNA network) in HCC. We found 177 cancer specific lncRNAs in HCC (fold change ≥ 1.5, P < 0.01), 41 of them were also discriminatively expressed with gender, race, tumor grade, AJCC tumor stage, and AJCC TNM staging system. Six lncRNAs (CECR7, LINC00346, MAPKAPK5-AS1, LOC338651, FLJ90757, and LOC283663) were found to be significantly associated with overall survival (OS, log-rank P < 0.05). Collectively, our results showed the lncRNA expression patterns and a complex ceRNA network in HCC, and identified a complex cancer specific ceRNA network, which includes 14 lncRNAs and 17 miRNAs in HCC.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Base Sequence
Carcinoma, Hepatocellular / genetics*
Carcinoma, Hepatocellular / mortality
Female
Gene Expression Regulation, Neoplastic / genetics*
Genetic Predisposition to Disease
Humans
Liver Neoplasms / genetics*
Liver Neoplasms / mortality
Male
RNA, Long Noncoding / biosynthesis
RNA, Long Noncoding / genetics*
Sequence Analysis, RNA

Substances

RNA, Long Noncoding

Grants and funding

This study was supported by Specialized Research Fund for the Doctoral Program of Higher Education and Research Grants Council Earmarked Research Grants Joint Research Scheme (No. M-CUHK406/13) and the National Natural Science Foundation of China (No. 81472339). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.