Please use this identifier to cite or link to this item: http://dx.doi.org/10.25673/34923
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dc.contributor.refereeHüttelmaier, Stefan-
dc.contributor.refereeKlussmann, Jan-Henning-
dc.contributor.refereePichler, Martin-
dc.contributor.authorPazaitis, Nikolaos-
dc.date.accessioned2020-11-04T13:17:48Z-
dc.date.available2020-11-04T13:17:48Z-
dc.date.issued2020-
dc.identifier.urihttps://opendata.uni-halle.de//handle/1981185920/35123-
dc.identifier.urihttp://dx.doi.org/10.25673/34923-
dc.description.abstractDas Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) gehört zu einer Familie onkofetaler RNA-bindender Proteine (RBP). Im Rahmen dieser kumulativen Arbeit zeigten wir, dass IGF2BP1 im hepatozellulären Karzinom im Vergleich zum normalen Lebergewebe das am höchsten exprimierte RBP ist. Seine Depletion führte zur Reduktion der Proliferation und zur Steigerung der Apoptose in Zellkulturen und zur Reduktion des Wachstums von xenograft-Tumoren im Mausmodell. Erklärend fanden wir eine durch IGF2BP1 vermittelte Stabilisierung des Protoonkogens MYC (myc proto-oncogene protein) und des Proliferationsmarkers MKI67 (marker of proliferation ki-67). Des Weiteren scheint IGF2BP1 im Rahmen der epitheliomesenchymalen-Transition durch Regulation des Transkriptionsfaktors LEF1 (lymphoid enhancer binding factor 1) einen positiven Einfluss auf die Zellmigration und möglicherweise die Metastasierung zu nehmen. IGF2BP1 ist somit als vielversprechendes Ziel zukünftiger Tumortherapien anzusehen.ger
dc.description.abstractThe insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) belongs to a family of oncofetal RNA binding proteins (RBPs). Here we demonstrate that IGF2BP1 is the most highly upregulated RBP in hepatocellular carcinoma compared to normal liver tissue. Its depletion resulted in reduced proliferation and enhanced apoptosis in cell cultures, as well as in an impairment of tumor growth in a murine xenograft model. As an explanation for the effects observed, we found that IGF2BP1 enhances the stability of the mRNAs of the proto-oncogene MYC (myc proto-oncogene protein) and the proliferation marker MKI67 (marker of proliferation ki-67). Furthermore IGF2BP1 seems to improve cell migration by stabilizing the transcription factor LEF1 (lymphoid enhancer binding factor 1) in the so called process of epithelial to mesenchymal transition and thus may be involved in the development of metastasis. The results suggest that IGF2BP1 is a promising target for future tumor therapies.eng
dc.format.extent1 Online-Ressource (132 Seiten)-
dc.language.isoger-
dc.rights.urihttp://rightsstatements.org/vocab/InC/1.0/-
dc.subject.ddc610-
dc.titleIn vitro und in vivo Untersuchungen zur Tumorigenität des Insulin-like growth factor 2 mRNA-binding protein 1 (IGF2BP1) : [kumulative Dissertation]ger
dcterms.dateAccepted2020-01-17-
dcterms.typeHochschulschrift-
dc.typePhDThesis-
dc.identifier.urnurn:nbn:de:gbv:3:4-1981185920-351235-
local.versionTypepublishedVersion-
local.publisher.universityOrInstitutionMartin-Luther-Universität Halle-Wittenberg-
local.subject.keywordsIGF2BP1 (Insulin-like growth factor 2 mRNA-binding protein 1), hepatozelluläres Karzinom (HCC), Ki-67 (marker of proliferation ki-67), MYC (myc proto-oncogene protein), epitheliomesenchymale Transition (EMT),LEF1 (lymphoid enhancer binding factor 1), xenografts, Tumorwachstum, shRNA (short hairpin-RNA), lentiviraler Gentransfer-
local.subject.keywordsIGF2BP1 (Insulin-like growth factor 2 mRNA-binding protein 1), hepatocellular carcinoma (HCC), Ki-67 (marker of proliferation ki-67), MYC (myc proto-oncogene protein), epithelial–mesenchymal transition (EMT),LEF1 (lymphoid enhancer binding factor 1), xenografts, tumor growth, shRNA (short hairpin-RNA), lentiviral gene transfer-
local.openaccesstrue-
dc.identifier.ppn1737769190-
local.publication.countryXA-DE-
cbs.sru.importDate2020-11-04T13:17:03Z-
local.accessrights.dnbfree-
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