title: MiR-7 triggers cell cycle arrest at the G1/S transition by targeting multiple genes including Skp2 and Psme3.
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 p27(KIP) 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.
authors.affiliation: National Institute for Cellular Biotechnology, Dublin City University, Dublin, Ireland.
authors.forename: Noelia
authors.initials: N
authors.lastname: Sanchez
authors.forename: Mark
authors.initials: M
authors.lastname: Gallagher
authors.forename: Nga
authors.initials: N
authors.lastname: Lao
authors.forename: Clair
authors.initials: C
authors.lastname: Gallagher
authors.forename: Colin
authors.initials: C
authors.lastname: Clarke
authors.forename: Padraig
authors.initials: P
authors.lastname: Doolan
authors.forename: Sinead
authors.initials: S
authors.lastname: Aherne
authors.forename: Alfonso
authors.initials: A
authors.lastname: Blanco
authors.forename: Paula
authors.initials: P
authors.lastname: Meleady
authors.forename: Martin
authors.initials: M
authors.lastname: Clynes
authors.forename: Niall
authors.initials: N
authors.lastname: Barron
mesh_terms: D000251:Adenosine Triphosphatases / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001324:Autoantigens / Q000235:genetics* / Q000378:metabolism; D016466:CHO Cells; D003412:Cricetulus; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics* / Q000378:metabolism; D059585:G1 Phase Cell Cycle Checkpoints / Q000235:genetics*; D005786:Gene Expression Regulation; D006801:Humans; D035683:MicroRNAs / Q000235:genetics* / Q000378:metabolism; D046988:Proteasome Endopeptidase Complex / Q000235:genetics* / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D044786:S-Phase Kinase-Associated Proteins / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013312:Stress, Physiological; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D001324:Autoantigens; C099558:Ki antigen; D035683:MicroRNAs; D044786:S-Phase Kinase-Associated Proteins; D016159:Tumor Suppressor Protein p53; D050760:Cyclin-Dependent Kinase Inhibitor p27; D051057:Proto-Oncogene Proteins c-akt; D046988:Proteasome Endopeptidase Complex; D000251:Adenosine Triphosphatases