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Comprehensive analysis of a ceRNA network reveals potential prognostic cytoplasmic lncRNAs involved in HCC progression.

Authors
  • Bai, Yi1
  • Long, Junyu1
  • Liu, Zhisong2
  • Lin, Jianzhen1
  • Huang, Hanchan1
  • Wang, Dongxu1
  • Yang, Xu1
  • Miao, Fei2
  • Mao, Yilei1
  • Sang, Xinting1
  • Zhao, Haitao1
  • 1 Department of Liver Surgery, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences & Peking Union Medical College (CAMS & PUMC), Beijing, China. , (China)
  • 2 Department of Statistics, Tianjin University of Finance and Economics Pearl River College, Tianjin, China. , (China)
Type
Published Article
Journal
Journal of Cellular Physiology
Publisher
Wiley (John Wiley & Sons)
Publication Date
Aug 01, 2019
Volume
234
Issue
10
Pages
18837–18848
Identifiers
DOI: 10.1002/jcp.28522
PMID: 30916406
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The aberrant expression of long noncoding RNAs (lncRNAs) has drawn increasing attention in the field of hepatocellular carcinoma (HCC) biology. In the present study, we obtained the expression profiles of lncRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) in 371 HCC tissues and 50 normal tissues from The Cancer Genome Atlas (TCGA) and identified hepatocarcinogenesis-specific differentially expressed genes (DEGs, log fold change ≥ 2, FDR < 0.01), including 753 lncRNAs, 97 miRNAs, and 1,535 mRNAs. Because the specific functions of lncRNAs are closely related to their intracellular localizations and because the cytoplasm is the main location for competitive endogenous RNA (ceRNA) action, we analyzed not only the interactions among these DEGs but also the distributions of lncRNAs (cytoplasmic, nuclear or both). Then, an HCC-associated deregulated ceRNA network consisting of 37 lncRNAs, 10 miRNAs, and 26 mRNAs was constructed after excluding those lncRNAs located only in the nucleus. Survival analysis of this network demonstrated that 15 lncRNAs, 3 miRNAs, and 16 mRNAs were significantly correlated with the overall survival of HCC patients (p < 0.01). Through multivariate Cox regression and lasso analysis, a risk score system based on 13 lncRNAs was constructed, which showed good discrimination and predictive ability for HCC patient survival time. This ceRNA network-construction approach, based on lncRNA distribution, not only narrowed the scope of target lncRNAs but also provided specific candidate molecular biomarkers for evaluating the prognosis of HCC, which will help expand our understanding of the ceRNA mechanisms involved in the early development of HCC. © 2019 The Authors. Journal of Cellular Physiology Published by Wiley Periodicals, Inc.

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