Characterization of SFPQ role in ovarian cancer cell lines
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ABSTRACT:
PROVIDER: PRJNA543992 | ENA |
REPOSITORIES: ENA
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Project description:SFPQ is a multifunctional nuclear protein first identified as a splicing factor, that participates in several cellular activities, including RNA transport, apoptosis and DNA repair. Here we report that SFPQ is a key mediator of platinum sensitivity in Epithelial Ovarian Cancer cell lines.
2019-08-31 | GSE131539 | GEO
Project description:Phenotypic characterisation of our zebrafish sfpq homozygous mutants revealed a restricted set of specific defects, unexpected for a protein expressed ubiquitously and involved in such general mechanisms. The CNS was prominently affected, showing brain boundary and axonal defects associated with absence of motility. To investigate a possible specificity in SFPQ functional targets by microarray RNA profiling analysis, comparing the transcriptome of the sfpq homozygous mutants with its wild type and heterozygous siblings at the earliest stage at which the phenotype is robustly recognizable.
2017-09-01 | E-MTAB-5559 | biostudies-arrayexpress
Project description:Characterization of three Epithelial Ovarian Cancer cell lines resistant to cisplatin.
| PRJNA362356 | ENA
Project description:Splicing factor proline and glutamine rich (SFPQ), DNA- and RNA binding protein, is crucial in various nuclear processes, including paraspeckle formation, miRNA synthesis and specially in transcription regulation. In addition, SFPQ play a role in the innate immune response to viruses, including DNA and RNA viruses. However, the connections between SFPQ and EMCV infection remain unclear. Here we report that the SFPQ is essential for EMCV replication. Depletion of SFPQ impairs EMCV production, while forced expression of SFPQ could promote viral replication. Mechanistically, EMCV inhibited viral RNA-mediated type I IFN and IL6 production to eliminate host antiviral immune responses. Cellular SFPQ was cleaved by the EMCV proteinase then entered the cytoplasm and interacted with other ribosomal proteins to facilitate its internal ribosome entry site (IRES)-dependent translation. Moreover, loss of SFPQ may impress host translation related gene expression and thus facilitate the EMCV replication. Altogether, our work provides a possible target for resisting EMCV or EMCV-like virus’s infection.
2019-01-10 | PXD011865 | Pride
Project description:To identify the RNA targets of the RNA binding proteins NONO and SFPQ in two different cell types, PARCLIP was carried out (Photoactivatable Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation) using a monoclonal antibody that recognises a NONO/SFPQ heterodimer. In this analysis, only the target gene NEAT1 was analysed, to show the binding sites for NONO and SFPQ in this transcript in the two cell lines.
2018-06-27 | GSE113349 | GEO
Project description:Philadelphia-like (Ph-like) acute lymphoblastic leukaemia (ALL) is a high-risk subtype of B-cell ALL characterised by a gene expression profile resembling Philadelphia Chromosome positive ALL (Ph+ ALL) in the absence of BCR-ABL1. Tyrosine kinase activating fusions, some involving ABL1, are recurrent drivers of Ph-like ALL and are targetable with tyrosine kinase inhibitors (TKIs). We identified a rare instance of SFPQ-ABL1 in a child with Ph-like ALL. SFPQ-ABL1 expressed in cytokine-dependent cell lines was sufficient to transform cells which were sensitive to ABL1-targeting TKIs. In contrast to BCR-ABL1, SFPQ-ABL1 localised to the nuclear compartment and was a weaker driver of cellular proliferation. Phosphoproteomics analysis showed upregulation of cell cycle, DNA replication and spliceosome pathways, and downregulation of signal transduction pathways, including ErbB, NF-kappa B, VEGF, and MAPK signalling in SFPQ-ABL1-, compared to BCR-ABL1-expressing cells. SFPQ-ABL1 expression did not activate PI3K/AKT signalling and was associated with phosphorylation of G2/M cell cycle proteins. SFPQ-ABL1 was sensitive to navitoclax and S-63845 and promotes cell survival through upregulation of Mcl-1 and Bcl-xL. SFPQ-ABL1 has functionally distinct mechanisms by which it drives ALL, including subcellular localisation, proliferative capacity, and activation of cellular pathways, highlighting the role that fusion partners have in mediating the function of ABL1 fusions.
2022-05-20 | PXD028925 | Pride
Project description:Purpose: We identified a rare instance of the SFPQ-ABL1 in a child with Ph-like ALL. The overall purpose of this study was to compare the structure and function of the SFPQ-ABL1 fusion to the well characterised BCR-ABL1 fusion. We used phosphoproteomics, transcriptomics and functional assays to determine the transforming capacity, subcellular localisation, and signalling networks of these two fusions. Given the known function of SFPQ in mRNA splicing, transcriptomic analysis was performed to analyse the effect of BCR-ABL1 or SFPQ-ABL1 expression on gene splicing. Methods: mRNA profiles of Ba/F3 cells expressing BCR-ABL1, SFPQ-ABL1, and empty vector control (MSCV) were generated by deep sequencing, in four biologically independent cell lines, using Illumina GAIIx. The sequences were aligned by subread and quantified by featureCounts. Results: In contrast to BCR-ABL1, SFPQ-ABL1 localised to the nuclear compartment and was a weaker driver of cellular proliferation. Phosphoproteomics analysis showed upregulation of cell cycle, DNA replication and spliceosome pathways, and downregulation of signal transduction pathways, including ErbB, NF-kappa B, VEGF, and MAPK signalling in SFPQ-ABL1-, compared to BCR-ABL1-expressing cells. SFPQ-ABL1 expression did not activate PI3K/AKT signalling and was associated with phosphorylation of G2/M cell cycle proteins. We identified no difference in overall splicing between cells expressing BCR-ABL1 and SFPQ-ABL1. Conclusions: SFPQ-ABL1 has functionally distinct mechanisms by which it drives ALL, including subcellular localisation, proliferative capacity, and activation of cellular pathways, highlighting the role that fusion partners have in mediating the function of ABL1 fusions.
2021-10-15 | GSE185860 | GEO
Project description:Epstein-Barr virus (EBV) uses a biphasic lifecycle of latency and lytic reactivation to infect >95% of adults worldwide. Despite its central role in EBV persistence and oncogenesis, much remains unknown about how EBV latency is maintained. We used a human genome-wide CRISPR/Cas9 screen to identify that the nuclear protein SFPQ was critical for latency. SFPQ supported expression of linker histone H1, which stabilizes nucleosomes and regulates nuclear architecture, but has not been previously implicated in EBV gene regulation. H1 occupied latent EBV genomes, including the immediate early gene BZLF1 promoter. Upon reactivation, SFPQ was sequestered into sub-nuclear puncta, and EBV genomic H1 occupancy diminished. Enforced H1 expression blocked EBV reactivation upon SFPQ knockout, confirming it as necessary downstream of SFPQ. SFPQ knockout triggered reactivation of EBV in B and epithelial cells as well as in Kaposi’s Sarcoma Associated Herpesvirus, suggesting a conserved gamma-herpesvirus role. These findings highlight SFPQ as a major regulator of H1 expression and EBV latency.
2024-04-16 | GSE235265 | GEO
Project description:MicroRNAs (miRNAs) play crucial roles in physiological functions and diseases such as cancer, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, revealed its proximity to SFPQ, a multifunctional RNA-binding protein (RBP) notably involved in forming the paraspeckle nuclear condensates. SFPQ depletion impacted both primary and mature miRNA expression, while other crucial paraspeckle proteins or the paraspeckle scaffolding lncRNA NEAT1 did not, indicating a unique paraspeckle-independent role. Comprehensive transcriptomic analyses showed that SFPQ loss broadly affects RNA and miRNA host gene (miRNA HG) expression, influencing both their transcription and stability. Notably, SFPQ protects specific miRNA HGs, including the oncogenic miR-17~92 polycistron, from degradation by the nuclear NEXT-exosome complex. Lastly, we show that high SFPQ is tightly linked with overexpression miR-17~92 and its mature miRNAs across a broad variety of cancers. Our findings reveal a dual role for SFPQ in the regulation of miRNA HGs transcription and stability, as well as its significance in cancers.
2024-09-04 | GSE262126 | GEO
Project description:MicroRNAs (miRNAs) play crucial roles in physiological functions and diseases such as cancer, but the regulation of their nuclear biogenesis remains poorly understood. Here, BioID on Drosha, the catalytic subunit of the microprocessor complex, revealed its proximity to SFPQ, a multifunctional RNA-binding protein (RBP) notably involved in forming the paraspeckle nuclear condensates. SFPQ depletion impacted both primary and mature miRNA expression, while other crucial paraspeckle proteins or the paraspeckle scaffolding lncRNA NEAT1 did not, indicating a unique paraspeckle-independent role. Comprehensive transcriptomic analyses showed that SFPQ loss broadly affects RNA and miRNA host gene (miRNA HG) expression, influencing both their transcription and stability. Notably, SFPQ protects specific miRNA HGs, including the oncogenic miR-17~92 polycistron, from degradation by the nuclear NEXT-exosome complex. Lastly, we show that high SFPQ is tightly linked with overexpression miR-17~92 and its mature miRNAs across a broad variety of cancers. Our findings reveal a dual role for SFPQ in the regulation of miRNA HGs transcription and stability, as well as its significance in cancers.
2024-09-04 | GSE262125 | GEO