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dc.contributor.authorBeheshti, Afshinen_US
dc.contributor.authorVanderburg, Charlesen_US
dc.contributor.authorMcDonald, J. Tysonen_US
dc.contributor.authorRamkumar, Charusheilaen_US
dc.contributor.authorKadungure, Tatendaen_US
dc.contributor.authorZhang, Hongen_US
dc.contributor.authorGartenhaus, Ronald B.en_US
dc.contributor.authorEvens, Andrew M.en_US
dc.date.accessioned2017-03-28T23:48:03Z
dc.date.issued2017en_US
dc.identifier.citationBeheshti, Afshin, Charles Vanderburg, J. Tyson McDonald, Charusheila Ramkumar, Tatenda Kadungure, Hong Zhang, Ronald B. Gartenhaus, and Andrew M. Evens. 2017. “A Circulating microRNA Signature Predicts Age-Based Development of Lymphoma.” PLoS ONE 12 (1): e0170521. doi:10.1371/journal.pone.0170521. http://dx.doi.org/10.1371/journal.pone.0170521.en
dc.identifier.issnen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:31731647
dc.description.abstractExtensive epidemiological data have demonstrated an exponential rise in the incidence of non-Hodgkin lymphoma (NHL) that is associated with increasing age. The molecular etiology of this remains largely unknown, which impacts the effectiveness of treatment for patients. We proposed that age-dependent circulating microRNA (miRNA) signatures in the host influence diffuse large B cell lymphoma (DLBCL) development. Our objective was to examine tumor development in an age-based DLBCL system using an inventive systems biology approach. We harnessed a novel murine model of spontaneous DLBCL initiation (Smurf2-deficient) at two age groups: 3 and 15 months old. All Smurf2-deficient mice develop visible DLBCL tumor starting at 15 months of age. Total miRNA was isolated from serum, bone marrow and spleen and were collected for all age groups for Smurf2-deficient mice and age-matched wild-type C57BL/6 mice. Using systems biology techniques, we identified a list of 10 circulating miRNAs being regulated in both the spleen and bone marrow that were present in DLBCL forming mice starting at 3 months of age that were not present in the control mice. Furthermore, this miRNA signature was found to occur circulating in the blood and it strongly impacted JUN and MYC oncogenic signaling. In addition, quantification of the miRNA signature was performed via Droplet Digital PCR technology. It was discovered that a key miRNA signature circulates throughout a host prior to the formation of a tumor starting at 3 months old, which becomes further modulated by age and yielded calculation of a ‘carcinogenic risk score’. This novel age-based circulating miRNA signature may potentially be leveraged as a DLBCL risk profile at a young age to predict future lymphoma development or disease progression as well as for potential innovative miRNA-based targeted therapeutic strategies in lymphoma.en
dc.language.isoen_USen
dc.publisherPublic Library of Scienceen
dc.relation.isversionofdoi:10.1371/journal.pone.0170521en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC5249061/pdf/en
dash.licenseLAAen_US
dc.subjectBiology and life sciencesen
dc.subjectGeneticsen
dc.subjectGene expressionen
dc.subjectGene regulationen
dc.subjectMicroRNAsen
dc.subjectBiochemistryen
dc.subjectNucleic acidsen
dc.subjectRNAen
dc.subjectNon-coding RNAen
dc.subjectExperimental Organism Systemsen
dc.subjectModel Organismsen
dc.subjectMouse Modelsen
dc.subjectAnimal Modelsen
dc.subjectBiology and Life Sciencesen
dc.subjectPhysiologyen
dc.subjectImmune Physiologyen
dc.subjectSpleenen
dc.subjectMedicine and Health Sciencesen
dc.subjectOncologyen
dc.subjectCancers and Neoplasmsen
dc.subjectHematologic Cancers and Related Disordersen
dc.subjectLymphomasen
dc.subjectHematologyen
dc.subjectBone Marrowen
dc.subjectImmunologyen
dc.subjectImmune Systemen
dc.subjectAnatomyen
dc.subjectBody Fluidsen
dc.subjectBlooden
dc.subjectMolecular Biologyen
dc.subjectMolecular Biology Techniquesen
dc.subjectArtificial Gene Amplification and Extensionen
dc.subjectPolymerase Chain Reactionen
dc.subjectCancer Risk Factorsen
dc.titleA Circulating microRNA Signature Predicts Age-Based Development of Lymphomaen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalPLoS ONEen
dash.depositing.authorVanderburg, Charlesen_US
dc.date.available2017-03-28T23:48:03Z
dc.identifier.doi10.1371/journal.pone.0170521*
dash.contributor.affiliatedVanderburg, Charles


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