Alteration of non-coding RNAs as a mechanism of lung cancer gene deregulation
department or school: Medicine, Faculty of
data provider: DSpace
degree campus: UBCV
creator: Stewart, Gregory
issued: 2020-04-14T16:20:20Z
issued: 2020
related degree: Doctor of Philosophy - PhD
degree grantor: University of British Columbia
description: Lung cancer remains the deadliest form of cancer, and less than half of lung adenocarcinoma (LUAD) patients harbour clinically actionable driver genes, emphasizing the need to explore alternative mechanisms of cancer gene deregulation. The advent of next generation sequencing has begun to reveal the functional importance of long non-coding RNAs (lncRNAs) in human cell biology, which can be exploited by tumours to drive the hallmarks of cancer. Due to their complex tertiary structure and unknown binding motifs there is a growing disparity between number of lncRNAs identified and those that have been functionally characterized. As such, lncRNAs deregulated in cancer may represent critical members of cancer pathways that could hold therapeutic applicability. The goal of this thesis is to identify lncRNAs important to LUAD biology, discover shared features and mechanisms used to regulate cancer driving protein coding genes, and evaluate the clinical relevance of these non-coding genes. We discover and investigate three major mechanisms harnesses by lncRNAs in LUAD: (i) cis-acting regulation of neighbouring genes, (ii) trans-acting regulation through sequence homology and (iii) regulation through shared miRNAs. This work uncovers evidence to suggest that alteration of lncRNAs is a major mechanism of cancer gene regulation in LUAD. Further characterization of these understudied gene regulatory mechanisms could lead to novel therapies that silence oncogenes or reactivate tumour suppressor genes.
aggregated CHO: https://circle.library.ubc.ca/rest/handle/2429/73990
note: ALTERATION OF NON-CODING RNAS AS A MECHANISM OF LUNG CANCER GENE DEREGULATION by GREGORY STEWART B.Sc, The University of Victoria, 2010 A THESIS SUBMITTED IN PARTIAL FULFILLMENT OF THE REQUIREMENTS FOR THE DEGREE OF DOCTOR OF PHILOSOPHY In THE FACULTY OF GRADUATE AND POSTDOCTORAL STUDIES (Interdisciplinary Oncology) THE UNIVERSITY OF BRITISH COLUMBIA (Vancouver) April 2020 © Gregory Stewart, 2020 ii The following individuals certify that they have read, and recommend to the Faculty of Graduate and Postdoctoral Studies for acceptance, the dissertation entitled: Alteration of non-coding RNAs as a mechanism of lung cancer gene deregulation submitted by Greg Stewart in partial fulfillment of the requirements for the degree of Doctor of Philosophy in Interdisciplinary Oncology Examining Committee: Dr. Wan Lam (Interdisciplinary Oncology) Supervisor Dr. Calum MacAulay (Pathology and Laboratory Medicine) Supervisory Committee Member Dr. Isabella Tai (Experimental Medicine) University Examiner Dr. Decheng Yang (Pathology and Laboratory Medicine) University Examiner Additional Supervisory Committee Members: Dr. Stephen Lam (Medicine) Supervisory Committee Member iii Abstract Lung cancer remains the deadliest form of cancer, and less than half of lung adenocarcinoma (LUAD) patients harbour clinically actionable driver genes, emphasizing the need to explore alternative mechanisms of cancer gene deregulation. The advent of next generation sequencing has begun to reveal the functional importance of long non-coding RNAs (lncRNAs) in human cell biology, which can be exploited by tumours to drive the hallmarks of cancer. Due to their complex tertiary structure and unknown binding motifs there is a growing disparity between number of lncRNAs identified and those that have been functionally characterized. As such, lncRNAs deregulated in cancer may represent critical members of cancer pathways that could hold therapeutic applicability. The goal of this thesis is to identify lncRNAs im…
has type: Thesis/Dissertation
date issued: 2020-05
is shown at: 10.14288/1.0389807
language: eng
degree discipline: Interdisciplinary Oncology
provider: Vancouver : University of British Columbia Library
publisher: University of British Columbia
rights: Attribution-NonCommercial-NoDerivatives 4.0 International
rights URI: http://creativecommons.org/licenses/by-nc-nd/4.0/
scholar level: Graduate
type: Text
identifier URI: http://hdl.handle.net/2429/73990