ITEM METADATA RECORD
Title: The role of microRNAs in the p53 pathway in ovarian cancer
Other Titles: De rol van microRNAs in de p53-signalisatieweg in eierstokkanker
Authors: Wynendaele, Jessica; S0222586
Issue Date: 5-Jun-2013
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mso-level-tab-stop:79.2pt; mso-level-number-position:left; margin-left:79.2pt; text-indent:-79.2pt;}ol {margin-bottom:0cm;}ul {margin-bottom:0cm;}-->Summary The risk ofdeveloping ovarian cancer is relatively low, however because of late diagnosis,it remains the deadliest gynecologic cancer. Treatment in late stages of thedisease results in most of the cases in drug resistance. Besides discoveringbiomarkers for early detection, gaining insights to the molecular mechanismsfundamental in acquiring drug resistance could contribute to better cancertreatment. p53 tumorsuppressor protein functions as a central response factor to most of cellularstresses and plays a pleiotropic role in protection against cancer. Itsimportance is underscored by the fact that half of human cancers have mutationsin the TP53 gene, whereas theremainder exhibits genetic or functional inactivation of genes that keep p53function at bay. These genes encode for proteins that influence p53 stabilityand/or activity either directly or indirectly and are often referred to as “negativep53-modulators”. Two main downstream negative regulators of p53 are MDM2 andMDM4. Increased expression levels of these proteins havebeen observed in manyhuman tumors ( Danovi et al 2004 yes">, Gembarska et al 2012 , Ragazzini et al 2004 ) . In addition toproteins, non-coding RNAs also play a major role in many biological processes,such as development, differentiation and proliferation and diseases. Theirimplication in tumorigenesis offers new avenues for diagnostic and anti-cancertherapeutic strategies. During my PhDstudies I aimed to investigte the potential role of selected microRNAs asregulators of p53 function and modifiers of ovarian cancerdevelopment/progression. During the course of these studies, we found acorrelation between one single polymorphism located in the 3’UTRof MDM4 andthe progression and chemosensitivity of ovarian cancer. Moreover, wedemonstrated that this SNP creates an illegitimate miR-191 target site, whichaffects MDM4 protein levels ( Wynendaele et al 2010 ) . Furthermore, weand others investigated a functional role for miR-605 in regulating p53 functionand stability ( Xiao et al 2011 yes">) . Weexplored miR-605’role in ovarian cancer development and response to therapy,and showed that miR-605 sensitizes ovarian cancer cells to the commonly usedanticancer drug, cisplatin, treatment.
Publication status: published
KU Leuven publication type: TH
Appears in Collections:Department of Human Genetics - miscellaneous

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