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Characterisation of the Splicing Factor, Proline- and Glutamine-Rich (SFPQ)-RNA interactome in melanoma and how it impacts the cancer phenotype

Bi, Omera (2020) Characterisation of the Splicing Factor, Proline- and Glutamine-Rich (SFPQ)-RNA interactome in melanoma and how it impacts the cancer phenotype. Doctoral thesis, University of Huddersfield.

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Abstract

There is emerging evidence linking aberrant expression of some long non-coding RNAs (lncRNAs) to cancer aetiology. Malignant melanoma (MM) is a lethal skin neoplasm, with the fastest rising incidence of all tumours and 5-year survival rates below 10%. Recently researchers have identified a role for the RNA-binding protein, Splicing Factor, Proline- and Glutamine-Rich (SFPQ) in several cancers, often via modulation of and interaction with long non-coding RNAs. The aim of this doctoral research project was to investigate (i) differentially expressed lncRNAs in melanoma and PMs (ii) identify novel SFPQ-lncRNA interactors via RIP-sequencing (seq) and determine the functional significance of these transcripts in melanoma (iii) establish if SFPQ contributes to the cancer phenotype in melanoma. RIP-seq uncovered a multitude of transcripts, including lncRNA, which specifically interacted with SFPQ in melanoma versus primary melanocytes (PM). Knockdown of these novel transcripts (LINC01234 and LINC00511) led to a decrease in cell migration and proliferation in melanoma cells. Additionally, depletion of SFPQ in melanoma cells, resulted in a reduction in cell migration, proliferation, metabolism, and an increase in apoptosis. Furthermore, clinical data suggest a direct link between increased expression of SFPQ and poor patient survival, suggesting that SFPQ may have some utility as a prognostic biomarker in melanoma.

Item Type: Thesis (Doctoral)
Uncontrolled Keywords: SFPQ, Malignant melanoma (MM), long non-coding RNA (lncRNA)
Subjects: Q Science > QH Natural history > QH301 Biology
R Medicine > RC Internal medicine > RC0254 Neoplasms. Tumors. Oncology (including Cancer)
Schools: School of Applied Sciences
Depositing User: Christine Morelli
Date Deposited: 02 Mar 2021 12:49
Last Modified: 28 Aug 2021 14:25
URI: http://eprints.hud.ac.uk/id/eprint/35447

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