Loss of miR-101 expression promotes Wnt/β-catenin signalling pathway activation and malignancy in colon cancer cells

J Pathol. 2013 Feb;229(3):379-89. doi: 10.1002/path.4097. Epub 2012 Nov 28.

Abstract

Colorectal cancer (CRC) is the second leading cause of cancer-related mortality in Western countries. Although the aberrant expression of several microRNAs (oncomiRs) is associated with CRC progression, the molecular mechanisms of this phenomenon are still under investigation. Here we show that miR-101 expression is differentially impaired in CRC specimens, depending on tumour grade. miR-101 re-expression suppresses cell growth in 3D, hypoxic survival and invasive potential in CRC cells showing low levels of miR-101. Additionally, we provide molecular evidence of a bidirectional regulatory mechanism between miR-101 expression and important CRC pro-malignant features, such as inflammation, activation of the Wnt/β-catenin signalling pathway and epithelial-mesenchymal transition (EMT). We then propose that up-regulated miR-101 may function as a tumour suppressor in CRC and that its pharmacological restoration might hamper the aggressive behaviour of CRC in vivo. MiR-101 expression may also represent a cancer biomarker for CRC diagnosis and prognosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / metabolism
  • Adenocarcinoma / pathology*
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Cell Hypoxia / physiology
  • Cell Line, Tumor
  • Cell Survival
  • Colorectal Neoplasms / genetics
  • Colorectal Neoplasms / metabolism
  • Colorectal Neoplasms / pathology*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Intestinal Mucosa / cytology
  • Intestinal Mucosa / metabolism
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Prognosis
  • Transfection
  • Up-Regulation
  • Wnt Proteins / metabolism*
  • Wnt Signaling Pathway / physiology*
  • beta Catenin / metabolism

Substances

  • Biomarkers, Tumor
  • MIRN101 microRNA, human
  • MicroRNAs
  • Wnt Proteins
  • beta Catenin