Genome-wide analysis of long noncoding RNA (lncRNA) expression in hepatoblastoma tissues

PLoS One. 2014 Jan 17;9(1):e85599. doi: 10.1371/journal.pone.0085599. eCollection 2014.

Abstract

Long noncoding RNAs (lncRNAs) have crucial roles in cancer biology. We performed a genome-wide analysis of lncRNA expression in hepatoblastoma tissues to identify novel targets for further study of hepatoblastoma. Hepatoblastoma and normal liver tissue samples were obtained from hepatoblastoma patients. The genome-wide analysis of lncRNA expression in these tissues was performed using a 4×180 K lncRNA microarray and Sureprint G3 Human lncRNA Chips. Quantitative RT-PCR (qRT-PCR) was performed to confirm these results. The differential expressions of lncRNAs and mRNAs were identified through fold-change filtering. Gene Ontology (GO) and pathway analyses were performed using the standard enrichment computation method. Associations between lncRNAs and adjacent protein-coding genes were determined through complex transcriptional loci analysis. We found that 2736 lncRNAs were differentially expressed in hepatoblastoma tissues. Among these, 1757 lncRNAs were upregulated more than two-fold relative to normal tissues and 979 lncRNAs were downregulated. Moreover, in hepatoblastoma there were 420 matched lncRNA-mRNA pairs for 120 differentially expressed lncRNAs, and 167 differentially expressed mRNAs. The co-expression network analysis predicted 252 network nodes and 420 connections between 120 lncRNAs and 132 coding genes. Within this co-expression network, 369 pairs were positive, and 51 pairs were negative. Lastly, qRT-PCR data verified six upregulated and downregulated lncRNAs in hepatoblastoma, plus endothelial cell-specific molecule 1 (ESM1) mRNA. Our results demonstrated that expression of these aberrant lncRNAs could respond to hepatoblastoma development. Further study of these lncRNAs could provide useful insight into hepatoblastoma biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Child
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic*
  • Gene Ontology
  • Gene Regulatory Networks
  • Genome, Human / genetics*
  • Hepatoblastoma / blood
  • Hepatoblastoma / genetics*
  • Humans
  • Liver Neoplasms / blood
  • Liver Neoplasms / genetics*
  • Male
  • RNA, Long Noncoding / genetics*
  • RNA, Long Noncoding / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics
  • Young Adult
  • alpha-Fetoproteins / metabolism

Substances

  • RNA, Long Noncoding
  • RNA, Messenger
  • alpha-Fetoproteins

Grants and funding

This study received financial support from the grant from the State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute (SKLORG #90-12-01). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.