CRNDE, a long-noncoding RNA, promotes glioma cell growth and invasion through mTOR signaling

Cancer Lett. 2015 Oct 28;367(2):122-8. doi: 10.1016/j.canlet.2015.03.027. Epub 2015 Mar 23.

Abstract

The transcripts of the gene Colorectal Neoplasia Differentially Expressed (CRNDE) are recognized as long-noncoding RNAs (lncRNAs), which are expressed in specific regions within the human brain, and are the most upregulated lncRNA in gliomas. However, the underlying regulation and function of CRNDE in gliomas are largely unknown. In this study, the upregulation of CRNDE was confirmed in both primary specimens from glioma patients and in vitro with cell lines. Overexpression of specific CRNDE transcript promotes cell growth and migration in vitro while knockdown of CRNDE expression manifests a repressive function during these cellular processes. The growth promoting effect of CRNDE was also demonstrated in a xenograft mouse model. Mechanistic studies further revealed that histone acetylation in the promoter region might account for the upregulation of CRNDE, and the level of CRNDE expression could be modulated by mammalian Target of Rapamycin (mTOR) signaling in glioma. Thus, our results shed a light on utilizing CRNDE as a potential novel therapeutic target for the treatment of glioma.

Keywords: CRNDE; Glioma; Histone modification; lncRNA; mTOR.

MeSH terms

  • Acetylation
  • Animals
  • Brain Neoplasms / genetics
  • Brain Neoplasms / metabolism*
  • Brain Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Movement*
  • Cell Proliferation*
  • Gene Expression Regulation, Neoplastic
  • Glioma / genetics
  • Glioma / metabolism*
  • Glioma / pathology
  • Histones / metabolism
  • Humans
  • Male
  • Mice, Inbred BALB C
  • Mice, Nude
  • Neoplasm Invasiveness
  • Promoter Regions, Genetic
  • RNA Interference
  • RNA, Long Noncoding / genetics
  • RNA, Long Noncoding / metabolism*
  • Signal Transduction*
  • TOR Serine-Threonine Kinases / metabolism*
  • Time Factors
  • Transfection
  • Tumor Burden
  • Up-Regulation

Substances

  • CRNDE RNA, human
  • Histones
  • RNA, Long Noncoding
  • MTOR protein, human
  • TOR Serine-Threonine Kinases