SFPQ promotes an oncogenic transcriptomic state in melanoma

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.

Development of Metabolic Synthetic Lethality and Its Implications for Thyroid Cancer

“…This screening approach highlights an underused approach to targeted therapeutic interference in BRAF -mutant colorectal cancer cells by exploiting the essential nuclear programs induced by MAPK activity identified in thyroid cancer cell lines. Consistent with the results in colon cancer cell lines, low expression of SFPQ is associated with decreased survival probability in The Cancer Genome Atlas (TCGA) dataset [ 54 ]. Further investigation of the role of SFPQ in the context of BRAF V600E -mutant thyroid cancer cells is required.…”

Establishment of an antibody specific for AMIGO2 improves immunohistochemical evaluation of liver metastases and clinical outcomes in patients with colorectal cancer

“…The association between organ carcinogenesis and AMIGO2 expression has been reported in various types of cancer, including gastric cancer [ 13 , 14 ], pancreatic cancer [ 20 ], colorectal cancer [ 11 , 19 ], breast cancer [ 12 ], ovarian cancer [ 17 ], endometrial cancer [ 21 ], melanoma [ 15 , 16 , 40 ], and pituitary neuroendocrine tumors [ 18 ]. Since AMIGO2 expression is involved not only in tumor development but also in tumor progression including acquisition of metastasis, AMIGO2 may be a new molecule that controls cancer stem cell-like function.…”

“…Furthermore, transcriptionally high levels of AMIGO2 are associated with shortened survival of patients with CRC [ 11 ], breast cancer [ 12 ], and gastric cancer [ 13 ]. AMIGO2 has been reported as a novel pathogenesis-related gene in gastric cancer [ 14 ], melanoma [ 15 , 16 ], ovarian cancer [ 17 ], and pituitary neuroendocrine tumors [ 18 ]. In addition, bioinformatics analysis using the transcriptome database selected AMIGO2 as a cancer-related gene candidate for CRC [ 19 ], pancreatic cancer [ 20 ], and endometrial cancer [ 21 ].…”

Inadvertent Transfer of Murine VL30 Retrotransposons to CAR-T Cells

“…However, various experimental systems demonstrated that the direction and mechanisms by which PSF/ncRNA complexes affect oncogenic pathways are cell type-dependent. [61][62][63][64][65] Similarly, notwithstanding the role of NEAT1 and PSF in inflammation and activation of the innate immune response [24,[66][67][68][69], paraspeckles' effects on viral infection are pathogen-specific. [24,57,64,[70][71][72][73][74][75] Based on the multiple mechanism by which PSF mediates its functions, it is difficult to predict the effects of VL30 mRNA expression on inflammatory (e.g., cytokine release) or oncogenic pathways in human T-cells.…”