MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma.

Hdl Handle:
http://hdl.handle.net/10147/132537
Title:
MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma.
Authors:
Tivnan, Amanda; Tracey, Lorraine; Buckley, Patrick G; Alcock, Leah C; Davidoff, Andrew M; Stallings, Raymond L
Affiliation:
Department of Cancer Genetics, Royal College of Surgeons in Ireland, York House, York Street, Dublin 2, Ireland.
Citation:
MicroRNA-34a is a potent tumor suppressor molecule in vivo in neuroblastoma. 2011, 11:33 BMC Cancer
Journal:
BMC cancer
Issue Date:
2011
URI:
http://hdl.handle.net/10147/132537
DOI:
10.1186/1471-2407-11-33
PubMed ID:
21266077
Additional Links:
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3038978/pdf/1471-2407-11-33.pdf
Abstract:
Neuroblastoma 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.; A 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).; Over 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.; We 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.
Item Type:
Article
Language:
en
MeSH:
Animals; Apoptosis; Blotting, Western; Cell Cycle; Cell Line, Tumor; Cell Proliferation; Genes, Tumor Suppressor; Humans; Luciferases; Luminescent Measurements; MAP Kinase Kinase Kinases; Mice; Mice, SCID; MicroRNAs; Neuroblastoma; Phosphoproteins; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Tumor Burden; Xenograft Model Antitumor Assays
ISSN:
1471-2407

Full metadata record

DC FieldValue Language
dc.contributor.authorTivnan, Amandaen
dc.contributor.authorTracey, Lorraineen
dc.contributor.authorBuckley, Patrick Gen
dc.contributor.authorAlcock, Leah Cen
dc.contributor.authorDavidoff, Andrew Men
dc.contributor.authorStallings, Raymond Len
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

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