dc.contributor.author | Sachrajda, Natalie | |
dc.date.accessioned | 2016-12-05T19:35:04Z | |
dc.date.available | 2016-12-05T19:35:04Z | |
dc.date.issued | 2016-12-05T19:35:04Z | |
dc.identifier.uri | http://hdl.handle.net/10222/72302 | |
dc.description.abstract | Kaposi’s sarcoma-associated herpesvirus (KSHV) is the infectious cause of Kaposi’s sarcoma (KS). KSHV has the ability to bypass a host anti-proliferative defense, oncogene-induced senescence (OIS), triggered by chronic oncogene expression. KSHV encodes 18
microRNAs (miRNAs) which are thought to fine-tune host gene expression to create a local pro-tumour environment in KS tissue. However, the functions of these miRNAs remain incompletely characterized. We identified two miRNAs, miR-K5 and miR-K11 that induced bypass of senescence. Senescence bypass coincided with marked reductions in levels of the p16 tumour suppressor, a key effector of the senescence program. miRNA-induced OIS bypass also coincided with alterations in γ-H2AX and 53BP1-positive DNA damage foci. Autophagic flux is required for efficient establishment of senescence. miR-K5 and miR-K11 inhibited flux in osteosarcoma cells. These data suggest that miR-K5 and miR-K11 may suppress OIS at multiple levels, thereby contributing to the ongoing proliferation of latently KSHV-infected cells. | en_US |
dc.language.iso | en | en_US |
dc.title | The Role of KSHV microRNAs in Bypass of Oncogene-Induced Senescence | en_US |
dc.date.defence | 2014-06-19 | |
dc.contributor.department | Department of Microbiology & Immunology | en_US |
dc.contributor.degree | Master of Science | en_US |
dc.contributor.external-examiner | Dr. Paola Marcato | en_US |
dc.contributor.graduate-coordinator | Dr. Brent Johnston | en_US |
dc.contributor.thesis-reader | Dr. Chris Richardson | en_US |
dc.contributor.thesis-reader | Dr. Patrick Lee | en_US |
dc.contributor.thesis-supervisor | Dr. Craig McCormick | en_US |
dc.contributor.ethics-approval | Not Applicable | en_US |
dc.contributor.manuscripts | Not Applicable | en_US |
dc.contributor.copyright-release | Not Applicable | en_US |