| Autor: |
Kwanghee Baek, Matthias Epple, Johannes H. Schulte, Sven Lindner, Sena Yoon, Shirley K. Knauer, Sarah Karczewski, A Bohrer, Jan J. Molenaar, Alexander Schramm, Anneleen Beckers, Franki Speleman, Angelika Eggert, Pieter Mestdagh, Kristina Althoff, Andrea Odersky, Diana Kozlova, Jo Vandesompele |
| Rok vydání: |
2014 |
| Předmět: |
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| Zdroj: |
International Journal of Cancer. 136:1308-1320 |
| ISSN: |
0020-7136 |
| Popis: |
MicroRNAs (miRNAs) are deregulated in a variety of human cancers, including neuroblastoma, the most common extracranial tumor of childhood. We previously reported a signature of 42 miRNAs to be highly predictive of neuroblastoma outcome. One miRNA in this signature, miR-542, was downregulated in tumors from patients with adverse outcome. Reanalysis of quantitative PCR and next-generation sequencing transcript data revealed that miR-542-5p as well as miR-542-3p expression is inversely correlated with poor prognosis in neuroblastoma patients. We, therefore, analyzed the function of miR-542 in neuroblastoma tumor biology. Ectopic expression of miR-542-3p in neuroblastoma cell lines reduced cell viability and proliferation, induced apoptosis and downregulated Survivin. Survivin expression was also inversely correlated with miR-542-3p expression in primary neuroblastomas. Reporter assays confirmed that miR-542-3p directly targeted Survivin. Downregulating Survivin using siRNA copied the phenotype of miR-542-3p expression in neuroblastoma cell lines, while cDNA-mediated ectopic expression of Survivin partially rescued the phenotype induced by miR-542-3p expression. Treating nude mice bearing neuroblastoma xenografts with miR-542-3p-loaded nanoparticles repressed Survivin expression, decreased cell proliferation and induced apoptosis in the respective xenograft tumors. We conclude that miR-542-3p exerts its tumor suppressive function in neuroblastoma, at least in part, by targeting Survivin. Expression of miR-542-3p could be a promising therapeutic strategy for treating aggressive neuroblastoma. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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