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

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.