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The Impact of HBO1 in Ovarian Cancer / Marcos Quintela Vazquez

DOI (Published version): 10.23889/Suthesis.49209

Abstract

New approaches to improve current detection and treatment of ovarian cancer (OC), now the fifth leading cause of cancer death among women in the United Kingdom, are increasingly needed. Current cytotoxic chemotherapy and targeted therapies have failed to significantly impact overall patient survival...

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Published: 2018
Institution: Swansea University
Degree level: Doctoral
Degree name: Ph.D
URI: https://cronfa.swan.ac.uk/Record/cronfa49209
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first_indexed 2019-03-14T20:00:41Z
last_indexed 2019-10-21T16:54:25Z
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spelling 2019-03-18T09:40:53.7943484 v2 49209 2019-03-14 The Impact of HBO1 in Ovarian Cancer 2019-03-14 New approaches to improve current detection and treatment of ovarian cancer (OC), now the fifth leading cause of cancer death among women in the United Kingdom, are increasingly needed. Current cytotoxic chemotherapy and targeted therapies have failed to significantly impact overall patient survival and drugs targeting epigenetic readers, writers and erasers are receiving much attention as potential sources of novel OC therapies. The identification of target molecules and/or epigenetic regulators with key roles in the OC phenotype and progression could facilitate the development of new effective treatment strategies. The main purpose of this study was to assess the role of the ‘histone acetyltransferase binding to ORC-1’ (HBO1), an epigenetic regulator that plays important roles in diverse molecular processes including DNA replication and transcription. Previous studies found HBO1 overexpressed in OC tissues and, although the molecular basis of its role is still unclear, it may represent a novel target involved in the modulation of the OC phenotype. To better understand the roles of HBO1 in OC, we first profiled its expression in cellular models and found it to be overexpressed compared to a non-cancerous cell model. Further analysis of the HBO1 downstream regulatory pathways through the use of two different silencing methodologies confirmed that HBO1 is involved in the regulation of important cancer associated pathways and processes, as well as individual oncogenes and tumour suppressor genes. Analysis of the biomechanical properties of OC cells using Atomic Force Microscopy outlined a role for HBO1 in the establishment of an aggressive cancerous phenotype, as the membranes of HBO1-overexpressing cells were significantly more elastic than their HBO1-depleted counterparts. Overall, the results of this study suggest dynamic roles for HBO1, which ought to be studied further to determine whether this molecule could be considered an attractive target for the future development of OC therapies. E-Thesis HBO1, Ovarian Cancer 31 12 2018 2018-12-31 10.23889/Suthesis.49209 A selection of third party content is redacted or is partially redacted from this thesis. COLLEGE NANME COLLEGE CODE Swansea University Doctoral Ph.D 2019-03-18T09:40:53.7943484 2019-03-14T16:29:40.0941297 Faculty of Medicine, Health and Life Sciences Swansea University Medical School - Medicine Marcos Quintela Vazquez 1 0049209-15032019130411.pdf QuintelaVazquez_Marcos_PhD_Final_Thesis_Redacted.pdf 2019-03-15T13:04:11.7200000 Output 41190797 application/pdf Redacted version - open access true 2019-03-14T00:00:00.0000000 true
title The Impact of HBO1 in Ovarian Cancer
spellingShingle The Impact of HBO1 in Ovarian Cancer
,
title_short The Impact of HBO1 in Ovarian Cancer
title_full The Impact of HBO1 in Ovarian Cancer
title_fullStr The Impact of HBO1 in Ovarian Cancer
title_full_unstemmed The Impact of HBO1 in Ovarian Cancer
title_sort The Impact of HBO1 in Ovarian Cancer
author ,
author2 Marcos Quintela Vazquez
format E-Thesis
publishDate 2018
institution Swansea University
doi_str_mv 10.23889/Suthesis.49209
college_str Faculty of Medicine, Health and Life Sciences
hierarchytype
hierarchy_top_id facultyofmedicinehealthandlifesciences
hierarchy_top_title Faculty of Medicine, Health and Life Sciences
hierarchy_parent_id facultyofmedicinehealthandlifesciences
hierarchy_parent_title Faculty of Medicine, Health and Life Sciences
department_str Swansea University Medical School - Medicine{{{_:::_}}}Faculty of Medicine, Health and Life Sciences{{{_:::_}}}Swansea University Medical School - Medicine
document_store_str 1
active_str 0
description New approaches to improve current detection and treatment of ovarian cancer (OC), now the fifth leading cause of cancer death among women in the United Kingdom, are increasingly needed. Current cytotoxic chemotherapy and targeted therapies have failed to significantly impact overall patient survival and drugs targeting epigenetic readers, writers and erasers are receiving much attention as potential sources of novel OC therapies. The identification of target molecules and/or epigenetic regulators with key roles in the OC phenotype and progression could facilitate the development of new effective treatment strategies. The main purpose of this study was to assess the role of the ‘histone acetyltransferase binding to ORC-1’ (HBO1), an epigenetic regulator that plays important roles in diverse molecular processes including DNA replication and transcription. Previous studies found HBO1 overexpressed in OC tissues and, although the molecular basis of its role is still unclear, it may represent a novel target involved in the modulation of the OC phenotype. To better understand the roles of HBO1 in OC, we first profiled its expression in cellular models and found it to be overexpressed compared to a non-cancerous cell model. Further analysis of the HBO1 downstream regulatory pathways through the use of two different silencing methodologies confirmed that HBO1 is involved in the regulation of important cancer associated pathways and processes, as well as individual oncogenes and tumour suppressor genes. Analysis of the biomechanical properties of OC cells using Atomic Force Microscopy outlined a role for HBO1 in the establishment of an aggressive cancerous phenotype, as the membranes of HBO1-overexpressing cells were significantly more elastic than their HBO1-depleted counterparts. Overall, the results of this study suggest dynamic roles for HBO1, which ought to be studied further to determine whether this molecule could be considered an attractive target for the future development of OC therapies.
published_date 2018-12-31T04:00:01Z
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score 11.037603

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