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.
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Accession codes
Abbreviations
- CDK:
-
cyclin-dependent kinase
- MCM:
-
mini-chromosome maintenance protein
- miRNA:
-
microRNA
- SA-ß-Gal:
-
senescence-associated ß-galactosidase
- siRNA:
-
short interfering RNA
- TP53 :
-
human p53 gene
- UTR:
-
untranslated region
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Acknowledgements
We thank Gabriele Becker and Yvonne Kahlert for excellent technical assistance, Filip Pattyn for critical remarks and Kathy Astrahantseff for proofreading the manuscript. This work was supported with Grants N2KR-S19T03 and 01GS0895 within NGFN-2 and NGFNPlus from the BMBF, and the EET-pipeline (No. 037260) and grant 259348 (ASSET) from the EU.
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Afanasyeva, E., Mestdagh, P., Kumps, C. et al. MicroRNA miR-885-5p targets CDK2 and MCM5, activates p53 and inhibits proliferation and survival. Cell Death Differ 18, 974–984 (2011). https://doi.org/10.1038/cdd.2010.164
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DOI: https://doi.org/10.1038/cdd.2010.164
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