Transcriptome profiling of lncRNA and co-expression networks in esophageal squamous cell carcinoma by RNA sequencing

Tumour Biol. 2016 Oct;37(10):13091-13100. doi: 10.1007/s13277-016-5227-3. Epub 2016 Jul 23.

Abstract

Long non-coding RNAs (lncRNAs) are emerging as crucial regulators of cancer. To identify novel targets for further study in esophageal squamous cell carcinoma (ESCC), we performed a genome-wide analysis of lncRNA expression in 12 ESCC tumor and normal tissues. Publicly available RNA-seq data were downloaded from the NCBI, GEO, and Co-LncRNA databases, and lncRNA and messenger RNA (mRNA) expression profiles were analyzed. In total, 127 lncRNAs were found to be differentially expressed, with a greater than fourfold change in ESCC tumor tissues compared with normal tissues. Among these lncRNAs, 98 were upregulated and 29 downregulated. Moreover, 1469 network nodes and 1720 connection edges between 119 lncRNAs and 1350 coding genes were integrated into the lncRNA and mRNA co-expression network. Bioinformatic analysis using GO terms revealed that these dysregulated lncRNAs are associated with developmental processes, proteinaceous extracellular matrix, and protein binding activity, with ECM-receptor interaction and the PI3K-Akt signaling pathway enrichment. Lastly, qRT-PCR results verified two significantly upregulated lncRNAs and three significantly downregulated lncRNAs in 50 pairs of ESCC tissues and adjacent normal tissues. These results reveal the landscape of ESCC-associated lncRNAs and co-expression networks, providing important insight regarding the lncRNAs involved in ESCC.

Keywords: Co-expression network; ESCC; Esophageal squamous cell carcinoma; Long non-coding RNA; lncRNA.

MeSH terms

  • Adult
  • Aged
  • Biomarkers, Tumor / genetics*
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Computational Biology
  • Esophageal Neoplasms / genetics*
  • Esophageal Neoplasms / pathology
  • Female
  • Follow-Up Studies
  • Gene Expression Profiling / methods*
  • Gene Expression Regulation, Neoplastic
  • Gene Regulatory Networks*
  • Humans
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Neoplasm Staging
  • Oligonucleotide Array Sequence Analysis
  • Prognosis
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • Real-Time Polymerase Chain Reaction
  • Retrospective Studies
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sequence Analysis, RNA / methods

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • RNA, Messenger