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dc.contributor.authorTivnan, Amanda
dc.contributor.authorTracey, Lorraine
dc.contributor.authorBuckley, Patrick G
dc.contributor.authorAlcock, Leah C
dc.contributor.authorDavidoff, Andrew M
dc.contributor.authorStallings, Raymond L
dc.date.accessioned2011-06-03T10:04:40Z
dc.date.available2011-06-03T10:04:40Z
dc.date.issued2011
dc.identifier.citationMicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. 2011, 11:33 BMC Canceren
dc.identifier.issn1471-2407
dc.identifier.pmid21266077
dc.identifier.doi10.1186/1471-2407-11-33
dc.identifier.urihttp://hdl.handle.net/10147/132537
dc.description.abstractNeuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system and accounts for 15% of childhood cancer mortalities. With regards to the role of miRNAs in neuroblastoma, miR-34a, mapping to a chromosome 1p36 region that is commonly deleted, has been found to act as a tumor suppressor through targeting of numerous genes associated with cell proliferation and apoptosis.
dc.description.abstractA synthetic miR-34a (or negative control) precursor molecule was transfected into NB1691luc and SK-N-ASluc neuroblastoma cells. Quantitative PCR was used to verify increased miR-34a levels in NB1691luc and SK-N-ASluc cell lines prior to in vitro and in vivo analysis. In vitro analysis of the effects of miR-34a over expression on cell growth, cell cycle and phosphoprotein activation in signal transduction pathways was performed. Neuroblastoma cells over expressing miR-34a were injected retroperitoneally into immunocompromised CB17-SCID mice and tumor burden was assessed over a 21 day period by measuring bioluminescence (photons/sec/cm²).
dc.description.abstractOver expression of miR-34a in both NB1691luc and SK-N-ASluc neuroblastoma cell lines led to a significant decrease in cell number relative to premiR-negative control treated cells over a 72 hour period. Flow cytometry results indicated that miR-34a induced cell cycle arrest and subsequent apoptosis activation. Phosphoprotein analysis highlighted key elements involved in signal transduction, whose activation was dysregulated as a result of miR-34a introduction into cells. As a potential mechanism of miR-34a action on phosphoprotein levels, we demonstrate that miR-34a over-expression results in a significant reduction of MAP3K9 mRNA and protein levels. Although MAP3K9 is a predicted target of miR-34a, direct targeting could not be validated with luciferase reporter assays. Despite this fact, any functional effects of reduced MAP3K9 expression as a result of miR-34a would be expected to be similar regardless of the mechanism involved. Most notably, in vivo studies showed that tumor growth was significantly repressed after exogenous miR-34a administration in retroperitoneal neuroblastoma tumors.
dc.description.abstractWe demonstrate for the first time that miR-34a significantly reduces tumor growth in an in vivo orthotopic murine model of neuroblastoma and identified novel effects that miR-34a has on phospho-activation of key proteins involved with apoptosis.
dc.language.isoenen
dc.relation.urlhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038978/pdf/1471-2407-11-33.pdfen
dc.subject.meshAnimals
dc.subject.meshApoptosis
dc.subject.meshBlotting, Western
dc.subject.meshCell Cycle
dc.subject.meshCell Line, Tumor
dc.subject.meshCell Proliferation
dc.subject.meshGenes, Tumor Suppressor
dc.subject.meshHumans
dc.subject.meshLuciferases
dc.subject.meshLuminescent Measurements
dc.subject.meshMAP Kinase Kinase Kinases
dc.subject.meshMice
dc.subject.meshMice, SCID
dc.subject.meshMicroRNAs
dc.subject.meshNeuroblastoma
dc.subject.meshPhosphoproteins
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction
dc.subject.meshSignal Transduction
dc.subject.meshTumor Burden
dc.subject.meshXenograft Model Antitumor Assays
dc.titleMicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma.en
dc.typeArticleen
dc.contributor.departmentDepartment of Cancer Genetics, Royal College of Surgeons in Ireland, York House, York Street, Dublin 2, Ireland.en
dc.identifier.journalBMC canceren
refterms.dateFOA2018-08-22T12:37:28Z
html.description.abstractNeuroblastoma is a paediatric cancer which originates from precursor cells of the sympathetic nervous system and accounts for 15% of childhood cancer mortalities. With regards to the role of miRNAs in neuroblastoma, miR-34a, mapping to a chromosome 1p36 region that is commonly deleted, has been found to act as a tumor suppressor through targeting of numerous genes associated with cell proliferation and apoptosis.
html.description.abstractA synthetic miR-34a (or negative control) precursor molecule was transfected into NB1691luc and SK-N-ASluc neuroblastoma cells. Quantitative PCR was used to verify increased miR-34a levels in NB1691luc and SK-N-ASluc cell lines prior to in vitro and in vivo analysis. In vitro analysis of the effects of miR-34a over expression on cell growth, cell cycle and phosphoprotein activation in signal transduction pathways was performed. Neuroblastoma cells over expressing miR-34a were injected retroperitoneally into immunocompromised CB17-SCID mice and tumor burden was assessed over a 21 day period by measuring bioluminescence (photons/sec/cm²).
html.description.abstractOver expression of miR-34a in both NB1691luc and SK-N-ASluc neuroblastoma cell lines led to a significant decrease in cell number relative to premiR-negative control treated cells over a 72 hour period. Flow cytometry results indicated that miR-34a induced cell cycle arrest and subsequent apoptosis activation. Phosphoprotein analysis highlighted key elements involved in signal transduction, whose activation was dysregulated as a result of miR-34a introduction into cells. As a potential mechanism of miR-34a action on phosphoprotein levels, we demonstrate that miR-34a over-expression results in a significant reduction of MAP3K9 mRNA and protein levels. Although MAP3K9 is a predicted target of miR-34a, direct targeting could not be validated with luciferase reporter assays. Despite this fact, any functional effects of reduced MAP3K9 expression as a result of miR-34a would be expected to be similar regardless of the mechanism involved. Most notably, in vivo studies showed that tumor growth was significantly repressed after exogenous miR-34a administration in retroperitoneal neuroblastoma tumors.
html.description.abstractWe demonstrate for the first time that miR-34a significantly reduces tumor growth in an in vivo orthotopic murine model of neuroblastoma and identified novel effects that miR-34a has on phospho-activation of key proteins involved with apoptosis.


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