Identification of long intergenic non-coding RNAs (lincRNAs) deregulated in gastrointestinal stromal tumors (GISTs)

PLoS One. 2018 Dec 17;13(12):e0209342. doi: 10.1371/journal.pone.0209342. eCollection 2018.

Abstract

Long intergenic non-coding RNAs (lincRNAs) are >200 nucleotides long non-coding RNAs, which have been shown to be implicated in carcinogenic processes by interacting with cancer associated genes or other non-coding RNAs. However, their role in development of rare gastrointestinal stromal tumors (GISTs) is barely investigated. Therefore, the aim of this study was to define lincRNAs deregulated in GIST and find new GIST-lincRNA associations. Next-generation sequencing data of paired GIST and adjacent tissue samples from 15 patients were subjected to a web-based lincRNA analysis. Three deregulated lincRNAs (MALAT1, H19 and FENDRR; adjusted p-value < 0.05) were selected for expression validation in a larger group of patients (n = 22) by RT-qPCR method. However, only H19 and FENDRR showed significant upregulation in the validation cohort (adjusted p < 0.05). Further, we performed correlation analyses between expression levels of deregulated lincRNAs and GIST-associated oncogenes or GIST deregulated microRNAs. We found high positive correlations between expression of H19 and known GIST related oncogene ETV1, and between H19 and miR-455-3p. These findings expand the knowledge on lincRNAs deregulated in GIST and may be an important resource for the future studies investigating lincRNAs functionally relevant to GIST carcinogenesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinogenesis / genetics*
  • DNA-Binding Proteins / genetics
  • Female
  • Gastrointestinal Neoplasms / genetics*
  • Gastrointestinal Neoplasms / pathology
  • Gastrointestinal Stromal Tumors / genetics*
  • Gastrointestinal Stromal Tumors / pathology
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Male
  • MicroRNAs / genetics
  • Middle Aged
  • RNA, Long Noncoding / analysis
  • RNA, Long Noncoding / metabolism*
  • Sequence Analysis, RNA
  • Transcription Factors / genetics

Substances

  • DNA-Binding Proteins
  • ETV1 protein, human
  • MIRN455 microRNA, human
  • MicroRNAs
  • RNA, Long Noncoding
  • Transcription Factors

Grants and funding

This work of UG and JS was supported by the Research Council of Lithuania (https://www.lmt.lt/en/) under the initiative of Researcher teams' projects, Grant no. MIP-006/2014. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.