Details

Autor(en) / Beteiligte

• 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

Titel

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

Ist Teil von

• Cell death and differentiation, 2011-06, Vol.18 (6), p.974-984

Ort / Verlag

London: Nature Publishing Group UK

Erscheinungsjahr

2011

Quelle

Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals

Beschreibungen/Notizen

• 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.