MiR-7 Triggers Cell Cycle Arrest at the G1/S Transition by Targeting Multiple Genes Including Skp2 and Psme3 |
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Authors: | Noelia Sanchez Mark Gallagher Nga Lao Clair Gallagher Colin Clarke Padraig Doolan Sinead Aherne Alfonso Blanco Paula Meleady Martin Clynes Niall Barron |
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Institution: | 1. National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.; 2. Conway Institute, University College Dublin, Dublin, Ireland.; CNRS UMR7275, France, |
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Abstract: | MiR-7 acts as a tumour suppressor in many cancers and abrogates proliferation of CHO cells in culture. In this study we demonstrate that miR-7 targets key regulators of the G1 to S phase transition, including Skp2 and Psme3, to promote increased levels of p27KIP and temporary growth arrest of CHO cells in the G1 phase. Simultaneously, the down-regulation of DNA repair-specific proteins via miR-7 including Rad54L, and pro-apoptotic regulators such as p53, combined with the up-regulation of anti-apoptotic factors like p-Akt, promoted cell survival while arrested in G1. Thus miR-7 can co-ordinate the levels of multiple genes and proteins to influence G1 to S phase transition and the apoptotic response in order to maintain cellular homeostasis. This work provides further mechanistic insight into the role of miR-7 as a regulator of cell growth in times of cellular stress. |
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