Targeting of integrin beta1 and kinesin 2alpha by microRNA 183

J Biol Chem. 2010 Feb 19;285(8):5461-71. doi: 10.1074/jbc.M109.037127. Epub 2009 Nov 24.

Abstract

MicroRNA 183 (miR-183) has been reported to inhibit tumor invasiveness and is believed to be involved in the development and function of ciliated neurosensory organs. We have recently found that expression of miR-183 increased after the induction of cellular senescence by exposure to H(2)O(2). To gain insight into the biological roles of miR-183 we investigated two potential novel targets: integrin beta1 (ITGB1) and kinesin 2alpha (KIF2A). miR-183 significantly decreased the expression of ITGB1 and KIF2A measured by Western blot. Targeting of the 3'-untranslated region (3'-UTR) of ITGB1 and KIF2A by miR-183 was confirmed by luciferase assay. Transfection with miR-183 led to a significant decrease in cell invasion and migration capacities of HeLa cells that could be rescued by expression of ITGB1 lacking the 3'-UTR. Although miR-183 had no effects on cell adhesion in HeLa cells, it significantly decreased adhesion to laminin, gelatin, and collagen type I in normal human diploid fibroblasts and human trabecular meshwork cells. These effects were also rescued by expression of ITGB1 lacking the 3'-UTR. Targeting of KIF2A by miR-183 resulted in some increase in the formation of cells with monopolar spindles in HeLa cells but not in human diploid fibroblast or human trabecular meshwork cells. The regulation of ITGB1 expression by miR-183 provides a new mechanism for the anti-metastatic role of miR-183 and suggests that this miRNA could influence the development and function in neurosensory organs, and contribute to functional alterations associated with cellular senescence in human diploid fibroblasts and human trabecular meshwork cells.

Publication types

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

MeSH terms

  • 3' Untranslated Regions / physiology*
  • Cell Adhesion / physiology
  • Cell Movement / physiology*
  • Fibroblasts / cytology
  • Fibroblasts / metabolism
  • Gene Expression Regulation / physiology*
  • HeLa Cells
  • Humans
  • Integrin beta1 / biosynthesis*
  • Integrin beta1 / genetics
  • Kinesin / biosynthesis*
  • Kinesin / genetics
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness
  • Neoplasm Metastasis
  • Trabecular Meshwork / cytology
  • Trabecular Meshwork / metabolism

Substances

  • 3' Untranslated Regions
  • Integrin beta1
  • KIF2A protein, human
  • MIRN183 microRNA, human
  • MicroRNAs
  • Kinesin