microRNA-17 Is the Most Up-Regulated Member of the miR-17-92 Cluster during Early Colon Cancer Evolution

PLoS One. 2015 Oct 14;10(10):e0140503. doi: 10.1371/journal.pone.0140503. eCollection 2015.

Abstract

Deregulated microRNAs play a role in the development and progression of colon cancer, but little is known about their tissue and cell distribution in the continuum of normal mucosa through the premalignant adenoma to invasive adenocarcinoma. The aim of this study was to examine the expression pattern of the miR-17-92 cluster (miR-17, miR-18, miR-19, miR-20 and miR-92) as well as miR-21, miR-31, miR-135b, and miR-145 in early clinically diagnosed colon cancer. MicroRNAs were analysed by chromogenic in situ hybridisation in the normal-adenoma-adenocarcinoma sequence of nine adenocarcinomas developed in mucosal colon polyps. Subsequently, the expression of selected microRNAs was validated in 24 mucosal colon cancer polyps. Expression of miR-17 was confined to the epithelial cells, and the expression levels increased in the transitional zone from normal to adenomatous tissue. The miR-17-92 cluster members, miR-19b, miR-20a, and miR-92a, followed the same expression pattern, but miR-17 was the most predominant. An increased expression of miR-21 was found in the tumour-associated stroma with the most dramatic increase from adenoma to adenocarcinoma, while the number of positive miR-145 fibroblast-like cells in the normal lamina propria (stroma) decreased in a stepwise manner throughout the normal-adenoma-adenocarcinoma sequence. It is concluded that the expression of miR-17, miR-21, and miR-145 changes at early stages of the normal-adenoma-adenocarcinoma sequence. Thus, these microRNAs may play a role in the development of colon cancer.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Transformation, Neoplastic / genetics*
  • Colonic Neoplasms / genetics*
  • Colonic Neoplasms / pathology*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • In Situ Hybridization
  • Male
  • MicroRNAs / genetics*
  • Molecular Imaging
  • Multigene Family*
  • Neoplasm Grading
  • Neoplasm Invasiveness
  • Neoplasm Staging
  • PTEN Phosphohydrolase / genetics
  • PTEN Phosphohydrolase / metabolism
  • Reproducibility of Results
  • beta Catenin / genetics

Substances

  • MIRN17 microRNA, human
  • MicroRNAs
  • beta Catenin
  • PTEN Phosphohydrolase

Grants and funding

The study was funded by Region of Southern Denmark’s PhD Fund (grant number 12/6786, http://www.regionsyddanmark.dk/wm325002), The University of Southern Denmark (www.sdu.dk), The Research Council of Lillebaelt Hospital (http://www.sygehuslillebaelt.dk/wm223295), King Christian X Foundation (http://kongehuset.dk/Menu/Fonde--legater/Kong-Christian-den-Tiendes-Fond/kong-christian-den-tiendesfond), The Family Spogaard Foundation (http://www.cancer.dk/forskning/stoette-til-forskning/familien-spogaards-fond/), Aase and Ejnar Danielsen Foundation (grant number 10-000789, http://www.danielsensfond.dk/Default.aspx), and Member of Parliament J. Christensen and wife K. Christensen Foundation. All grants mentioned above were given to KNK. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. BSN is employed by a commercial company (Bioneer A/S, Denmark). The funder provided support in form of salary, but did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.