Temporal expression and functional analysis of long non-coding RNAs in colorectal cancer initiation

J Cell Mol Med. 2019 Jun;23(6):4127-4138. doi: 10.1111/jcmm.14300. Epub 2019 Mar 28.

Abstract

Long non-coding RNAs (lncRNAs) have potential applications in clinical diagnosis and targeted cancer therapies. However, the expression profile of lncRNAs in colorectal cancer (CRC) initiation is still unclear. In this study, the expression profiles of lncRNAs and mRNAs were determined by microarray at specific tumour stages in an AOM/DSS-induced primary colon cancer model. The temporal expression of lncRNAs was analysed by K-means clustering. Additionally, weighted correlation network analysis (WGCNA) and gene ontology analysis were performed to construct co-expression networks and establish functions of the identified lncRNAs and mRNAs. Our results suggested that 4307 lncRNAs and 5798 mRNAs are deregulated during CRC initiation. These differential expression genes (DEGs) exhibited a clear correlation with the differential stage of tumour initiation. WGCNA results suggested that a series of hub lncRNAs are involved in regulating cell stemness, colon inflammation, oxidative stress response and cell death at each stage. Among them, lncRNA H19 was up-regulated in colon tumours and correlated with poor patient prognosis. Collectively, we have been the first to demonstrate the temporal expression and function of lncRNAs in CRC initiation. These results provide novel diagnosis and therapy targets for CRC.

Keywords: H19; colorectal cancer; expression profile; long noncoding RNAs; temporal expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Death / genetics
  • Cell Transformation, Neoplastic / genetics
  • Colorectal Neoplasms / genetics*
  • Gene Expression Profiling / methods
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Ontology
  • Gene Regulatory Networks / genetics
  • Humans
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neoplasm Staging / methods
  • Oxidative Stress / genetics
  • RNA, Long Noncoding / genetics*
  • RNA, Messenger / genetics
  • Up-Regulation / genetics

Substances

  • RNA, Long Noncoding
  • RNA, Messenger