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AuthorPelzer, Christindc.contributor.author
Date of accession2017-03-31T06:10:09Zdc.date.accessioned
Available in OPARU since2017-03-31T06:10:09Zdc.date.available
Year of creation2016dc.date.created
Date of first publication2017-03-31dc.date.issued
AbstractRecently, our team identified FOXO1 to be a tumor suppressor in classical Hodgkin Lymphoma (cHL). Its tumor suppressive activities arise from its function as transcription factor regulating the expression of various genes involved in cell cycle and apoptosis. Our previous studies showed that FOXO1 is downregulated in cHL by diverse mechanisms including dysregulated AKT and ERK signaling, as well as chromosomal aberrations. Re-introduction of FOXO1 leads to cell cycle arrest and apoptosis in cHL cell lines. Within the last couple of years increasing evidence suggested that altered microRNA expression is associated with various disease states, such as cancer. In this study, we show that FOXO1 is repressed by miR-96, miR-182 and 183 in classical Hodgkin Lymphoma. These three miRNAs are differentially expressed in cHL cell lines, functional experiments using a luciferase reporter assay confirm that the these miRNAs specifically target the 3'UTR of FOXO1 and the application of specific anti-miRs leads to an increased level of FOXO1 protein for all three miRNAs. MiR-96, miR-182 and miR-183 are located in very close genomic proximity to each other, sharing the same transcription start site and thereby leading to a cooperative repression of the tumor suppressive transcription factor FOXO1. However, our data was obtained from only EBV negative cHL cell lines. Another study has shown that the EBV derived protein LMP1 downregulates the miR-183/96/182 cluster, which in turn could mean that our findings might only apply for EBV negative cases (approx. 60%). Novel therapies pursue the goal of targeting oncogenic miRNAs. Therefore, the miR-183/96/182 cluster could possibly be a suitable target for new therapy approaches in cHL.dc.description.abstract
Languageen_USdc.language.iso
PublisherUniversität Ulmdc.publisher
LicenseStandarddc.rights
Link to license texthttps://oparu.uni-ulm.de/xmlui/license_v3dc.rights.uri
KeywordFOXO1dc.subject
KeywordcHLdc.subject
KeywordmiR-96dc.subject
KeywordmiR-182dc.subject
KeywordmiR-183dc.subject
KeywordClassical Hodgkin lymphomadc.subject
Dewey Decimal GroupDDC 610 / Medicine & healthdc.subject.ddc
MeSHForkhead transcription factorsdc.subject.mesh
MeSHMicroRNAsdc.subject.mesh
MeSHHodgkin diseasedc.subject.mesh
TitleThe role of microRNA in FOXO1 repression in classical Hodgkin Lymphomadc.title
Resource typeDissertationdc.type
Date of acceptance2016-12-16dcterms.dateAccepted
RefereeWirth, Thomasdc.contributor.referee
RefereeBarth, Thomasdc.contributor.referee
DOIhttp://dx.doi.org/10.18725/OPARU-4288dc.identifier.doi
PPN885179196dc.identifier.ppn
URNhttp://nbn-resolving.de/urn:nbn:de:bsz:289-oparu-4327-0dc.identifier.urn
GNDForkhead-Box-Proteinedc.subject.gnd
GNDmiRNSdc.subject.gnd
GNDLymphogranulomatosedc.subject.gnd
FacultyMedizinische Fakultätuulm.affiliationGeneral
InstitutionInstitut für Physiologische Chemieuulm.affiliationSpecific
InstitutionUKU. Institut für Pathologieuulm.affiliationSpecific
Shelfmark print versionW: W-H 15.071uulm.shelfmark
Grantor of degreeMedizinische Fakultätuulm.thesisGrantor
DCMI TypeTextuulm.typeDCMI
TypeErstveröffentlichunguulm.veroeffentlichung
CategoryPublikationenuulm.category
University Bibliographyjauulm.unibibliographie


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