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Title: Characterisation of circulating extracellular microRNAs and development of a method for their absolute quantification
Author: Brown, Eoin
ISNI:       0000 0004 6060 9889
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2016
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MicroRNAs (miRNAs) are a class of small non-coding RNAs that regulate gene expression at the post transcriptional level. miRNAs are known to exist extracellularly in a stable manner; the stability of these miRNAs in the extracellular environment has been attributed to their protection within extracellular vesicles (EVs). EVs are a class of membrane encapsulated vesicles released from cells, with an important role in mediating intracellular communication. This thesis set out to assess the therapeutic potential in vascular disease of the population of EVs released by endothelial colony forming cells (ECFCs), a sub-population of circulating cells with known pro-angiogenic potential, and specifically in the role of their miRNA cargo. Characterisation of ECFC-derived EVs found that ECFCs release a diverse population of EVs that can interact with and may alter the migratory potential of recipient cells. The miRNA expression profile of ECFCs and their EVs was assessed via high throughput sequencing, demonstrating distinct expression profiles between compartments. Variations in the sequence of expressed miRNAs were ubiquitous. These miRNA variants are termed isomiRs and like the mature miRNAs, exhibited a distinct expression pattern between ECFCs and their derived EVs. The mechanism(s) directing miRNA export are not yet fully understood; examining the sequence of exported isomiRs it was determined that aspects of their sequence may influence export. With their remarkable stability, circulating miRNAs are proving to be of great potential as non-invasive biomarkers. The profiling of circulating isomiRs, particularly with the use of a novel method of assessing their expression as a proportion of their reference miRNA, highlighted the additional information that can be gained from their inclusion. To utilise the additional information to be gained from the inclusion of isomiR expression profiles in the use of miRNAs as biomarkers, an assay (IsoSeq) was developed to enable the unbiased quantification of isomiR expression profile for specific miRNAs of interest.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available