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dc.contributor.authorMissiaglia, E
dc.contributor.authorShepherd, CJ
dc.contributor.authorAladowicz, E
dc.contributor.authorOlmos, D
dc.contributor.authorSelfe, J
dc.contributor.authorPierron, G
dc.contributor.authorDelattre, O
dc.contributor.authorWalters, Z
dc.contributor.authorShipley, J
dc.date.accessioned2017-01-05T10:55:19Z
dc.date.issued2017-01
dc.identifier.citationCancer letters, 2017, 385 pp. 251 - 260
dc.identifier.issn0304-3835
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/372
dc.identifier.eissn1872-7980
dc.identifier.doi10.1016/j.canlet.2016.10.011
dc.description.abstractRhabdomyosarcomas (RMS) in children and adolescents are heterogeneous sarcomas broadly defined by skeletal muscle features and the presence/absence of PAX3/7-FOXO1 fusion genes. MicroRNAs are small non-coding RNAs that regulate gene expression in a cell context specific manner. Sequencing analyses of microRNAs in 64 RMS revealed expression patterns separating skeletal muscle, fusion gene positive and negative RMS. Integration with parallel gene expression data assigned biological functions to 12 co-expression networks/modules that reassuringly included myogenic roles strongly correlated with microRNAs known in myogenesis and RMS development. Modules also correlated with clinical outcome and fusion status. Regulation of microRNAs by the fusion protein was demonstrated after PAX3-FOXO1 reduction, exemplified by miR-9-5p. MiR-9-5p levels correlated with poor outcome, even within fusion gene positive RMS, and were higher in metastatic versus non-metastatic disease. MiR-9-5p reduction inhibited RMS cell migration. Our findings reveal microRNAs in a regulatory framework of biological and clinical significance in RMS.
dc.formatPrint-Electronic
dc.format.extent251 - 260
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
dc.subjectCell Line, Tumor
dc.subjectHumans
dc.subjectRhabdomyosarcoma, Alveolar
dc.subjectRhabdomyosarcoma, Embryonal
dc.subjectNeoplasm Invasiveness
dc.subjectGenetic Predisposition to Disease
dc.subjectOncogene Proteins, Fusion
dc.subjectMicroRNAs
dc.subjectReproducibility of Results
dc.subjectGene Fusion
dc.subjectGene Expression Profiling
dc.subjectTransfection
dc.subjectComputational Biology
dc.subjectCell Movement
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectPhenotype
dc.subjectDatabases, Genetic
dc.subjectPaired Box Transcription Factors
dc.subjectGene Regulatory Networks
dc.subjectHigh-Throughput Nucleotide Sequencing
dc.subjectBiomarkers, Tumor
dc.titleMicroRNA and gene co-expression networks characterize biological and clinical behavior of rhabdomyosarcomas.
dc.typeJournal Article
dcterms.dateAccepted2016-10-03
rioxxterms.versionofrecord10.1016/j.canlet.2016.10.011
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by-nc-nd/4.0
rioxxterms.licenseref.startdate2017-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfCancer letters
pubs.notesNo embargo
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology
pubs.organisational-group/ICR
pubs.organisational-group/ICR/Primary Group
pubs.organisational-group/ICR/Primary Group/ICR Divisions
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Cancer Therapeutics/Sarcoma Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Sarcoma Molecular Pathology
pubs.publication-statusPublished
pubs.volume385
pubs.embargo.termsNo embargo
icr.researchteamSarcoma Molecular Pathologyen_US
dc.contributor.icrauthorWalters, Zoeen
dc.contributor.icrauthorShipley, Janeten
dc.contributor.icrauthorSelfe, Joannaen


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