27116545 | PURPOSE: The purpose of this study was to investigate the mechanisms by which miR-183 may contribute to the phenotypic alterations associated with stress-induced senescence of human trabecular meshwork (HTM) cells |
27116545 | METHODS: Changes in gene expression induced by miR-183 in HTM cells were evaluated by gene array analysis, confirmed by quantitative-PCR (Q-PCR), and analyzed by MetaCore pathway analysis |
27116545 | A plasmid expressing KIAA0101 without its 3'-untranslated region (3'-UTR) was cotransfected with miR-183 to evaluate the role of KIAA0101 on the effects induced by miR-183 |
27116545 | RESULTS: miR-183 affected the expression of multiple genes involved in cell cycle regulation and DNA damage response in HTM cells |
27116545 | Forced expression of miR-183 in HTM and HDF resulted in a significant decrease in proliferation in primary HTM and HDF cells but not in HeLa cells |
27116545 | In all cell types tested, overexpression of miR-183 resulted in increased DNA damage under UV irradiation |
27116545 | CONCLUSIONS: Our results suggest that the observed up-regulation of miR-183 after stress-induced senescence in HTM cells may contribute to reinforce cellular senescence by inhibiting cell cycle progression through multiple gene targets and limiting the DNA repair mechanisms through inhibition of KIAA0101 |
19940135 | Targeting of integrin beta1 and kinesin 2alpha by microRNA 183 |
19940135 | 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 |
19940135 | We have recently found that expression of miR-183 increased after the induction of cellular senescence by exposure to H(2)O(2) |
19940135 | To gain insight into the biological roles of miR-183 we investigated two potential novel targets: integrin beta1 (ITGB1) and kinesin 2alpha (KIF2A) |
19940135 | Targeting of the 3'-untranslated region (3'-UTR) of ITGB1 and KIF2A by miR-183 was confirmed by luciferase assay |
19940135 | 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 |
19940135 | 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 |
19940135 | 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 |
19940135 | 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 |