Systematic study of novel lncRNAs in different gastrointestinal cancer cells

Discov Med. 2016 Mar;21(115):159-71.

Abstract

Background: Recently, many lncRNAs were found to be deregulated in various human cancers and play important roles in carcinogenesis.

Material and methods: To investigate the association of lncRNAs to gastrointestinal cancers, 12 cases of esophageal cancer and hepatic cancer, 16 cases of gastric cancer and colorectal cancer and their matched adjacent tissue samples, 12 esophageal cancer cell lines, 7 gastric cancer cell lines, 10 colorectal cancer cell lines, and 11 hepatic cancer cell lines were examined. RNA-seq, bioinformatics pipeline, co-expression network, and gene ontology enrichment analysis were performed.

Results: We have identified 23,169 candidate novel lncRNA transcripts. Comparing with protein coding genes the lncRNAs tend to be shorter and have less exons. Remarkably, we found 15 lncRNAs that were down-regulated in all cancer cell lines among all four types of cancers. In addition, we analyzed the differentially expressed lncRNAs in gastrointestinal cancer cells before and after treatment with 5-Aza. Many lncRNAs were up-regulated after 5-Aza treatment, which suggested that the expression of these lncRNAs may be regulated by DNA methylation. Finally, based on the co-expression network and GO enrichment analysis, we predicted that many novel lncRNAs were involved in pathways like apoptosis, cell cycle, cell adhesion, EMT, epigenetic regulation, DNA damage response signaling, and immune response.

Conclusion: Based on RNA-Seq and bioinformatics analysis, we have identified a significant number of novel lncRNAs, which could be involved in important pathways related to gastrointestinal cancer development. Overall, we provide a rich resource for identifying new biomarkers and studying novel lncRNA regulation pathways in gastrointestinal cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics
  • Azacitidine / pharmacology
  • Biomarkers, Tumor / genetics
  • Carcinogenesis / genetics*
  • Cell Cycle / genetics
  • Cell Line, Tumor
  • DNA Methylation
  • Down-Regulation
  • Epigenesis, Genetic
  • Epithelial-Mesenchymal Transition / genetics
  • Gastrointestinal Neoplasms / genetics*
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • RNA, Long Noncoding / drug effects
  • RNA, Long Noncoding / genetics*
  • Real-Time Polymerase Chain Reaction
  • Sequence Analysis, RNA
  • Signal Transduction / genetics*
  • Up-Regulation

Substances

  • Biomarkers, Tumor
  • RNA, Long Noncoding
  • Azacitidine