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CRNDE, a long non-coding RNA responsive to insulin/IGF signaling, regulates genes involved in central metabolism

Blake C Ellis1, Lloyd D Graham1, Peter L Molloy1

  • 1CSIRO Animal, Food and Health Sciences, Preventative Health Flagship, Commonwealth Scientific and Industrial Research Organization, Sydney, NSW 2113 Australia.

Biochimica Et Biophysica Acta
|November 5, 2013
PubMed

Insights

Colorectal neoplasia differentially expressed (CRNDE) long non-coding RNA is regulated by insulin signaling in colorectal cancer. CRNDE nuclear transcripts influence cellular metabolism and the Warburg effect, potentially driving cancer progression.

Area of Science:

  • Molecular Biology
  • Cancer Research
  • Epigenetics

Background:

  • Colorectal neoplasia differentially expressed (CRNDE) is an emerging gene implicated in early colorectal cancer development.
  • CRNDE transcripts function as long non-coding RNAs (lncRNAs), potentially mediating epigenetic regulation of gene expression.
  • The precise regulation and functional roles of CRNDE in cancer remain largely uncharacterized.

Purpose of the Study:

  • To investigate the regulatory mechanisms of CRNDE expression in colorectal cancer.
  • To identify novel CRNDE transcripts and elucidate their functional significance.
  • To explore the role of CRNDE in mediating cellular metabolic reprogramming, specifically the Warburg effect.

Main Methods:

  • Identification and characterization of novel CRNDE transcripts, including those with a conserved sequence in intron 4 (gVC-In4).
  • Treatment of colorectal cancer cells with insulin and insulin-like growth factors (IGF) and pathway inhibitors (PI3K/Akt/mTOR, Raf/MAPK).
  • siRNA-mediated knockdown of gVC-In4 transcripts followed by expression array analyses to assess gene expression changes.

Main Results:

  • Insulin/IGF treatment repressed CRNDE nuclear transcripts, an effect reversed by PI3K/Akt/mTOR and Raf/MAPK pathway inhibitors, indicating CRNDE is a downstream target.
  • Knockdown of gVC-In4 transcripts altered the expression of genes involved in insulin/IGF signaling, glucose, and lipid metabolism.
  • Affected genes overlapped with those modulated by insulin treatment, suggesting a role for CRNDE in metabolic regulation.

Conclusions:

  • CRNDE nuclear transcripts are regulated by insulin/IGF signaling pathways in colorectal cancer cells.
  • CRNDE plays a role in promoting metabolic alterations, including the Warburg effect, characteristic of cancer cells.
  • These findings highlight a novel function for lncRNAs in regulating cellular metabolism and suggest CRNDE as a potential therapeutic target in colorectal cancer.
Keywords:
CRCCRNDEColorectal cancerColorectal neoplasia differentially expressedGenomic vertebrate conserved in intron 4IGF1IGF1RIGF2INSRIPAIngenuity Pathway AnalysisInsulinInsulin receptorInsulin-like growth factor 1Insulin-like growth factor 1 receptorInsulin-like growth factor 2Long non-coding RNAMAPKMammalian target of rapamycinMitogen activated protein kinasePI3KPhosphatidylinositide 3-kinaseTCATricarboxylic acidWarburg effectgVC-In4lncRNAmTOR

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