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dc.contributor.authorRees, Evan
dc.contributor.otherQueen's University (Kingston, Ont.). Theses (Queen's University (Kingston, Ont.))en
dc.date2012-07-09 12:32:35.235en
dc.date.accessioned2012-07-09T22:03:09Z
dc.date.available2012-07-09T22:03:09Z
dc.date.issued2012-07-09
dc.identifier.urihttp://hdl.handle.net/1974/7318
dc.descriptionThesis (Master, Pathology & Molecular Medicine) -- Queen's University, 2012-07-09 12:32:35.235en
dc.description.abstractCutaneous melanoma is an increasingly common aggressive malignancy. The molecular mechanisms responsible for melanoma’s initiation and progression are still unclear, but new evidence suggests microRNAs (miRNAs) may be involved. MicroRNAs are small non-coding RNAs that have been shown to act as either oncogenes or tumour suppressors. These short, ~22 nucleotide long, single stranded RNA molecules regulate gene expression post-transcriptionally, through complementary binding to target messenger RNA (mRNA), and mediate mRNA degradation and translational repression. Our laboratory has previously shown that miRNA expression levels are altered through the different stages of melanoma tumourigenesis and has identified numerous significantly dysregulated miRNAs. miR-205 expression is significantly decreased in both primary and metastatic melanoma. Because of this decrease in miR-205 level with increasing cancer aggressiveness, we originally hypothesized that miR-205 may act as a tumour suppressor in melanoma. Unexpectedly, miR-205 re-expression in metastatic melanoma cells has shown oncogenetic potential. Through functional assays, we determined that miR-205 plays a primary role in promoting cellular migration and invasion, and in repressing adhesion. A gene expression analysis was conducted and the target prediction algorithm TargetScan was utilized to determine potential mRNA targets for miR-205. CADM1, PTPRJ and SHIP2 were three of the targets investigated, because of their known functional role in migration and cellular adhesion. CADM1 and PTPRJ were both verified to be directly targeted by miR-205 in an in vitro melanoma system using a luciferase reporter assay. In summary, we have demonstrated a surprising functional role for miR-205 in melanoma. The re-expression of miR-205 promotes malignant phenotypes and therefore is functioning with oncogenic potential within our metastatic melanoma cell culture system.en_US
dc.languageenen
dc.language.isoenen_US
dc.relation.ispartofseriesCanadian thesesen
dc.rightsThis publication is made available by the authority of the copyright owner solely for the purpose of private study and research and may not be copied or reproduced except as permitted by the copyright laws without written authority from the copyright owner.en
dc.subjectmiR-205en_US
dc.subjectMicroRNAen_US
dc.subjectMelanomaen_US
dc.titleMicroRNA-205 Involvement in Cutaneous Melanomaen_US
dc.typeThesisen_US
dc.description.degreeMasteren
dc.contributor.supervisorTron, Victoren
dc.contributor.departmentPathology and Molecular Medicineen


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