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SFPQ promotes an oncogenic transcriptomic state in melanoma
O Bi1, C A Anene2, J Nsengimana3
1School of Applied Sciences, University of Huddersfield, Huddersfield, UK.
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.
Insights
Splicing factor, proline- and glutamine-rich (SFPQ) protein drives melanoma by interacting with oncogenic RNAs. Lowering SFPQ slows cancer growth, migration, and impacts key melanoma-associated genes, suggesting SFPQ as a prognostic biomarker.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Splicing factor, proline- and glutamine-rich (SFPQ) is linked to various cancers via RNA interactions.
- The specific role of SFPQ in melanoma pathogenesis is not well understood.
Purpose of the Study:
- To investigate the function and molecular mechanisms of SFPQ in melanoma.
- To evaluate SFPQ as a potential prognostic biomarker for melanoma.
Main Methods:
- SFPQ knockdown in melanoma cells.
- RNA immunoprecipitation sequencing (RIP-seq) to identify SFPQ-RNA interactions.
- Functional assays for cell growth, migration, EMT, apoptosis, and glycolysis.
- Analysis of clinical melanoma patient cohorts.
Main Results:
- SFPQ knockdown inhibited melanoma cell growth, migration, epithelial-mesenchymal transition, apoptosis, and glycolysis.
- RIP-seq revealed a reprogrammed SFPQ-RNA interactome in melanoma, enriched with oncogenic transcripts like SOX10, AMIGO2, and LINC00511.
- SFPQ is essential for the expression of several melanoma-associated coding and long non-coding RNAs (lncRNAs).
- lncRNAs LINC00511 and LINC01234 promote melanoma phenotypes, with LINC00511 modulating the miR-625-5p/PKM2 axis.
- Elevated SFPQ expression in primary tumors correlates with melanoma prognosis.
Conclusions:
- SFPQ acts as a significant driver of melanoma progression through RNA interactions that enhance oncogenic transcript expression.
- SFPQ and its associated lncRNAs represent potential therapeutic targets and prognostic biomarkers in melanoma.
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