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dc.contributor.authorLi Santi, Anna
dc.date.accessioned2017-09-08T12:23:06Z
dc.date.available2017-09-08T12:23:06Z
dc.date.issued2016-12-14
dc.identifier.urihttp://hdl.handle.net/10556/2468
dc.identifier.urihttp://dx.doi.org/10.14273/unisa-868
dc.description2014 - 2015it_IT
dc.description.abstractThe urokinase type plasminogen activator (uPAR) is a three domain GPI-anchored cell surface receptor. uPAR expression is strongly up-regulated and represents a negative prognostic factor in various tumors, including hematologic malignancies. uPAR expression is post-transcriptionally regulated by RNA binding proteins (RBPs). RBPs bind specific sequences in the 3’untranslated region (3’UTR) of uPAR-mRNA, stabilizing or destabilizing the transcript. The 3’UTR of transcripts from a large number of genes includes target sequences also for small translational repressors RNAs (miRNAs). miRNAs play key roles in many cellular pathways; their aberrant expression is a common feature of various malignancies. We selected three miRNAs miR-146a, miR-335 and miR-622 that could bind the 3’UTR of uPAR-mRNA; these three miRNAs, as reported in literature, are expressed in CD34+ HSC or in acute myeloid leukemia (AML) cells and can act as oncosuppressors by inhibiting oncogene expression. We found that selected miRNAs regulate uPAR expression by directly targeting its 3’UTR in AML cell lines. Indeed, uPAR expression is reduced by their overexpression and increased by their specific inhibitors. Overexpression of selected miRNAs impaired cell migration, invasion and proliferation of AML cell lines. Interestingly, we found an inverse relationship between uPAR expression and miR- 146a and miR-335 levels in AML blasts. This suggests their possible role in regulating uPAR expression also in vivo. We also investigated the capability of uPAR-3’UTR to act as competing endogenous RNA (ceRNA). We showed that uPAR-3’UTR overexpression up-regulates uPAR expression and expression of other targets of selected miRNAs; these results suggest that uPAR-3’UTR may recruit selected miRNAs, allowing translation of their targets, thus acting as ceRNA. [edited by Author]it_IT
dc.language.isoitit_IT
dc.publisherUniversita degli studi di Salernoit_IT
dc.subjectUrochinasiit_IT
dc.subjectuPARit_IT
dc.subjectmiRNAit_IT
dc.subjectceRNAit_IT
dc.titleRegolazione post-trascrizionale dell’espressione del recettore dell’urochinasiit_IT
dc.typeDoctoral Thesisit_IT
dc.subject.miurBIO/13 BIOLOGIA APPLICATA MED/04 PATOLOGIA GENERALEit_IT
dc.contributor.coordinatoreLeone, Antoniettait_IT
dc.description.cicloXIV n.s.it_IT
dc.contributor.tutorRagno, Piait_IT
dc.identifier.DipartimentoFarmaciait_IT
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