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

Frank Westermann (1) , Elena Afanasyeva (1) , Pieter Mestdagh (1) , Candy Kumps (1) , Jo Vandesompele (1) , Volker Ehemann (1) , Jessika Theissen (1) , Matthias Fischer (1) , Marc Zapatka (1) , Benedikt Brors (1) , Larissa Savelyeva (1) , Vitaliya Sagulenko (1) , Frank Speleman (1) , Manfred Schwab (1)

1 Department of Tumor Genetics

Several miRNA loci are found within genomic regions frequently deleted in primary neuroblastoma, including miR-885-5p at 3p25.3. Here we demonstrate that miR-885-5p is downregulated upon 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 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 CDK2 and MCM5. Both genes are targeted by miR-885-5p via predicted binding sites within the 3'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.

Mots clés: 3p25.3; miRNA; p53 stabilization; senescence

Frank Westermann, Elena Afanasyeva, Pieter Mestdagh, Candy Kumps, Jo Vandesompele, et al.. MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death and Differentiation, 2011, ⟨10.1038/cdd.2010.164⟩. ⟨hal-00608714⟩