Fusion genes and lncRNAs in prostate cancer

: a comparison in men of African and European descent

Abstract

Men of African descent are significantly more likely to be affected by prostate cancer (PC) in their lifetime, with earlier onset, increased disease aggression and elevated mortality rates compared to men of European descent. The origins of these differences are typically accredited to a complex interplay involving socioeconomic factors, environmental exposures, and underlying genetic differences. Long non-coding RNAs (lncRNAs). lncRNAs are defined as transcripts longer than 200 nucleotides and not coding for proteins. Traditionally they were considered transcriptional noise with no biological significance. It has since been determined that lncRNAs can regulate gene expression through a series of regulatory mechanisms.

In parallel with the emerging recognition of lncRNAs as cancer biomarkers, fusion genes have firmly established themselves as biomarkers for a variety of cancers. A fusion gene can be described as the joining of two genes which results in its transcription and translation as a hybrid gene. These hybrid genes can generate novel proteins with tumorigenic functions.

The occurrence of vitamin D deficiency is significantly more common in individuals of African descent compared to European descent. Two factors directly contribute to this observed difference; 1. the lack of a nutritionally rich vitamin D diet and 2. higher skin pigmentation. Individuals with darker skin tones have higher levels of melanin present in their skin, a pigment which absorbs and scatters ultraviolet-B radiation thus making it more difficult for individuals of African descent to produce enough vitamin D. Using systems and network biology approaches, this thesis provides a thorough examination of PC racial differences in the areas of the regulatory role of lncRNAs, fusion genes and the effects of vitamin D supplementation on the lncRNA transcriptome. This was completed using two distinct high-quality datasets which encompassed varying stages of localised PC between patients of African and European descent.

Thesis is embargoed until 31 July 2027.

Date of Award	Jul 2024
Original language	English
Awarding Institution	Queen's University Belfast
Supervisor	Gary Hardiman (Supervisor) & Emma Allott (Supervisor)