MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival
- 14 January 2011
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cell Death & Differentiation
- Vol. 18 (6), 974-984
- https://doi.org/10.1038/cdd.2010.164
Abstract
Several microRNA (miRNA) loci are found within genomic regions frequently deleted in primary neuroblastoma, including miR-885-5p at 3p25.3. In this study, we demonstrate that miR-885-5p is downregulated on loss of 3p25.3 region in neuroblastoma. Experimentally enforced miR-885-5p expression in neuroblastoma cell lines inhibits proliferation triggering cell cycle arrest, senescence and/or apoptosis. miR-885-5p leads to the accumulation of p53 protein and activates the p53 pathway, resulting in upregulation of p53 targets. Enforced miR-885-5p expression consistently leads to downregulation of cyclin-dependent kinase (CDK2) and mini-chromosome maintenance protein (MCM5). Both genes are targeted by miR-885-5p via predicted binding sites within the 3′-untranslated regions (UTRs) of CDK2 and MCM5. Transcript profiling after miR-885-5p introduction in neuroblastoma cells reveals alterations in expression of multiple genes, including several p53 target genes and a number of factors involved in p53 pathway activity. Taken together, these data provide evidence that miR-885-5p has a tumor suppressive role in neuroblastoma interfering with cell cycle progression and cell survival.Keywords
This publication has 36 references indexed in Scilit:
- miR-331-3p Regulates ERBB-2 Expression and Androgen Receptor Signaling in Prostate CancerJournal of Biological Chemistry, 2009
- Inactivation of CDK2 is synthetically lethal to MYCN over-expressing cancer cellsProceedings of the National Academy of Sciences, 2009
- New miRNAs cloned from neuroblastomaBMC Genomics, 2008
- The microRNA.org resource: targets and expressionNucleic Acids Research, 2007
- Transactivation of miR-34a by p53 Broadly Influences Gene Expression and Promotes ApoptosisMolecular Cell, 2007
- MicroRNA-34a functions as a potential tumor suppressor by inducing apoptosis in neuroblastoma cellsOncogene, 2007
- The von Hippel-Lindau tumor suppressor gene expression level has prognostic value in neuroblastomaInternational Journal of Cancer, 2006
- MicroRNA expression profiles classify human cancersNature, 2005
- Conserved Seed Pairing, Often Flanked by Adenosines, Indicates that Thousands of Human Genes are MicroRNA TargetsCell, 2005
- Myc suppression of the p21Cip1 Cdk inhibitor influences the outcome of the p53 response to DNA damageNature, 2002