MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival

Afanasyeva, E. A., Mestdagh, P., Kumps, C., Vandesompele, J., Ehemann, V., Theissen, J., Fischer, M., Zapatka, M., Brors, B., Savelyeva, L., Sagulenko, V., Speleman, F., Schwab, M. and Westermann, F. (2011) MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death and Differentiation, 18 6: 974-984. doi:10.1038/cdd.2010.164

Author Afanasyeva, E. A.
Mestdagh, P.
Kumps, C.
Vandesompele, J.
Ehemann, V.
Theissen, J.
Fischer, M.
Zapatka, M.
Brors, B.
Savelyeva, L.
Sagulenko, V.
Speleman, F.
Schwab, M.
Westermann, F.
Title MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival
Journal name Cell Death and Differentiation   Check publisher's open access policy
ISSN 1350-9047
Publication date 2011-06-18
Sub-type Article (original research)
DOI 10.1038/cdd.2010.164
Volume 18
Issue 6
Start page 974
End page 984
Total pages 11
Place of publication London, Hampshire, U.K.
Publisher Nature Publishing Group
Collection year 2012
Language eng
Formatted 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.
Keyword Senescence
p53 Stabilization
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Non HERDC
School of Chemistry and Molecular Biosciences
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Created: Thu, 20 Oct 2011, 09:52:43 EST by Vitaliya Sagulenko on behalf of School of Chemistry & Molecular Biosciences