Targeting of Integrin beta 1 and Kinesin 2 alpha by miR-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 H2O2. To gain insight into the biological roles of miR-183 we investigated two potential novel targets: integrin beta 1 (ITGB1) and kinesin 2 alpha (KIF2A). MiR183 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 the 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 (HDF) and human trabecular meshwork (HTM) 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 HDF or HTM 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 HDF and HTM cells.