| Autor: |
Kristina, Althoff, Sven, Lindner, Andrea, Odersky, Pieter, Mestdagh, Anneleen, Beckers, Sarah, Karczewski, Jan J, Molenaar, Anna, Bohrer, Shirley, Knauer, Frank, Speleman, Matthias, Epple, Diana, Kozlova, Sena, Yoon, Kwanghee, Baek, Jo, Vandesompele, Angelika, Eggert, Alexander, Schramm, Johannes H, Schulte |
| Rok vydání: |
2013 |
| Předmět: |
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| Zdroj: |
International journal of cancer. 136(6) |
| ISSN: |
1097-0215 |
| 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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