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miR-542-3p exerts tumor suppressive functions in neuroblastoma by downregulating Survivin

(2015) INTERNATIONAL JOURNAL OF CANCER. 136(6). p.1308-1320
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Abstract
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. What's new? The profile of microRNAs in a tumor can help predict the severity of the disease. Neuroblastomas with poor outcome have been shown to contain less of miR-542-3p. In this paper, the authors investigated this microRNA's function and found that it downregulates the protein Survivin, an apoptosis inhibitor. When the authors delivered nanoparticles bearing miR-542-3p to human neuroblastomas in mice, the treatment slowed Survivin production, induced apoptosis, and stopped tumor growth. Thus, miR-542-3p appears to hold promise for treating this often deadly childhood tumor.
Keywords
Survivin, neuroblastoma, miR-542-3p, nanoparticles, AURORA-B, CHROMOSOME 1P, MICRORNAS, EXPRESSION, CELLS, MYCN, CANCER, YM155, APOPTOSIS, ONCOGENE

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Chicago
Althoff, Kristina, Sven Lindner, Andrea Odersky, Pieter Mestdagh, Anneleen Beckers, Sarah Karczewski, Jan J Molenaar, et al. 2015. “miR-542-3p Exerts Tumor Suppressive Functions in Neuroblastoma by Downregulating Survivin.” International Journal of Cancer 136 (6): 1308–1320.
APA
Althoff, K., Lindner, S., Odersky, A., Mestdagh, P., Beckers, A., Karczewski, S., Molenaar, J. J., et al. (2015). miR-542-3p exerts tumor suppressive functions in neuroblastoma by downregulating Survivin. INTERNATIONAL JOURNAL OF CANCER, 136(6), 1308–1320.
Vancouver
1.
Althoff K, Lindner S, Odersky A, Mestdagh P, Beckers A, Karczewski S, et al. miR-542-3p exerts tumor suppressive functions in neuroblastoma by downregulating Survivin. INTERNATIONAL JOURNAL OF CANCER. 2015;136(6):1308–20.
MLA
Althoff, Kristina, Sven Lindner, Andrea Odersky, et al. “miR-542-3p Exerts Tumor Suppressive Functions in Neuroblastoma by Downregulating Survivin.” INTERNATIONAL JOURNAL OF CANCER 136.6 (2015): 1308–1320. Print.
@article{5661021,
  abstract     = {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. 
What's new? The profile of microRNAs in a tumor can help predict the severity of the disease. Neuroblastomas with poor outcome have been shown to contain less of miR-542-3p. In this paper, the authors investigated this microRNA's function and found that it downregulates the protein Survivin, an apoptosis inhibitor. When the authors delivered nanoparticles bearing miR-542-3p to human neuroblastomas in mice, the treatment slowed Survivin production, induced apoptosis, and stopped tumor growth. Thus, miR-542-3p appears to hold promise for treating this often deadly childhood tumor.},
  author       = {Althoff, Kristina and Lindner, Sven and Odersky, Andrea and Mestdagh, Pieter and Beckers, Anneleen and  Karczewski, Sarah and Molenaar, Jan J and Bohrer, Anna and Knauer, Shirley and Speleman, Franki and Epple, Matthias and Kozlova, Diana and Yoon, Sena and Baek, Kwanghee and Vandesompele, Jo and Eggert, Angelika and Schramm, Alexander and Schulte, Johannes H},
  issn         = {0020-7136},
  journal      = {INTERNATIONAL JOURNAL OF CANCER},
  keyword      = {Survivin,neuroblastoma,miR-542-3p,nanoparticles,AURORA-B,CHROMOSOME 1P,MICRORNAS,EXPRESSION,CELLS,MYCN,CANCER,YM155,APOPTOSIS,ONCOGENE},
  language     = {eng},
  number       = {6},
  pages        = {1308--1320},
  title        = {miR-542-3p exerts tumor suppressive functions in neuroblastoma by downregulating Survivin},
  url          = {http://dx.doi.org/10.1002/ijc.29091},
  volume       = {136},
  year         = {2015},
}

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