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SFPQ promotes an oncogenic transcriptomic state in melanoma

2021; Springer Nature; Volume: 40; Issue: 33 Linguagem: Inglês

10.1038/s41388-021-01912-4

1476-5594

Omera Bi, Chinedu Anthony Anene, Jérémie Nsengimana, M. Shelton, Wayne Roberts, Julia Newton‐Bishop, James R. Boyne,

RNA modifications and cancer

Abstract The multifunctional protein, splicing factor, proline- and glutamine-rich (SFPQ) has been implicated in numerous cancers often due to interaction with coding and non-coding RNAs, however, its role in melanoma remains unclear. We report that knockdown of SFPQ expression in melanoma cells decelerates several cancer-associated cell phenotypes, including cell growth, migration, epithelial to mesenchymal transition, apoptosis, and glycolysis. RIP-seq analysis revealed that the SFPQ-RNA interactome is reprogrammed in melanoma cells and specifically enriched with key melanoma-associated coding and long non-coding transcripts, including SOX10, AMIGO2 and LINC00511 and in most cases SFPQ is required for the efficient expression of these genes. Functional analysis of two SFPQ-enriched lncRNA, LINC00511 and LINC01234 , demonstrated that these genes independently contribute to the melanoma phenotype and a more detailed analysis of LINC00511 indicated that this occurs in part via modulation of the miR-625-5p/ PKM2 axis. Importantly, analysis of a large clinical cohort revealed that elevated expression of SFPQ in primary melanoma tumours may have utility as a prognostic biomarker. Together, these data suggest that SFPQ is an important driver of melanoma, likely due to SFPQ–RNA interactions promoting the expression of numerous oncogenic transcripts.