Аннотация
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.
- 2,
- 3'
- base
- biosynthesis/genetics;
- cell
- cells,
- cultured;
- cycle
- cyclin-dependent
- deletion;
- down-regulation,
- expression
- gene
- genetic
- genetics/metabolism
- genetics/metabolism;
- genetics;
- humans;
- kinase
- line,
- loci;
- micrornas,
- neoplasm,
- neoplastic,
- neuroblastoma,
- p53,
- proliferation;
- protein
- proteins,
- regions,
- regulation,
- rna,
- sequence
- sequence;
- suppressor
- survival;
- tumor
- tumor;
- untranslated
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