A combined literature and in silico analysis enlightens the role of the NDRG family in the gut

Biochim Biophys Acta Gen Subj. 2018 Oct;1862(10):2140-2151. doi: 10.1016/j.bbagen.2018.07.004. Epub 2018 Jul 7.

Abstract

Background: The N-Myc Downstream-Regulated Gene (NDRG) family comprises four members that function in cellular processes like proliferation and differentiation. While NDRG1 and NDRG2 are extensively studied, knowledge regarding NDRG3 and NDRG4, despite its recognition as a well-established early-detection marker for colorectal cancer (Cologuard®), is sparse.

Scope of review: To summarize expression, biomarker potential and functional mechanisms of the NDRGs in the developing, mature and cancerous gut, we combine current literature and in silico analyses from the TCGA-database, GTEX Project, E14.5 mouse intestine and enteric neural crest cells, and an RNA-sequencing time-series of human embryonic colonic samples.

Major conclusions: This study reveals that all members display a differential expression pattern in the gut and that NDRG1, NDRG2 and NDRG4 (1) can serve as biomarker for colorectal cancer and (2) have tumor suppressive properties mainly affecting cell proliferation and epithelial-mesenchymal transition.

General significance: Similar effects of the NDRGs on the key-hallmarks of cancer, could implicate analogous functions in other tissue/cancer types.

Keywords: Biomarkers; Colorectal cancer; Intestinal tract; N-myc downstream-regulated gene; Tumor suppressors.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Cycle Proteins / metabolism*
  • Computer Simulation
  • Epithelial-Mesenchymal Transition*
  • Gastrointestinal Neoplasms / metabolism
  • Gastrointestinal Neoplasms / pathology*
  • Humans
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Muscle Proteins / metabolism*
  • Nerve Tissue Proteins / metabolism*
  • Review Literature as Topic
  • Tumor Suppressor Proteins / metabolism*

Substances

  • Cell Cycle Proteins
  • Intracellular Signaling Peptides and Proteins
  • Muscle Proteins
  • N-myc downstream-regulated gene 1 protein
  • NDRG2 protein, human
  • NDRG3 protein, human
  • NDRG4 protein, human
  • Nerve Tissue Proteins
  • Tumor Suppressor Proteins