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SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells

ABSTRACT: SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells

PROVIDER: PRJNA628515 | ENA |

REPOSITORIES: ENA

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SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells II

Project description:Oncoproteins such as the BRAFV600E kinase entrust cancer cells with malignant properties, but they also create unique vulnerabilies. Therapeutic targeting of the BRAFV600E-driven cytoplasmic signaling network has proven ineffective, since patients regularly relapse with reactivation of the targeted signaling pathways. Here, we identified the nuclear protein SFPQ to be synthetically lethal with BRAFV600E in a loss-of-function shRNA screen. SFPQ depletion decreased proliferation and induced apoptosis in BRAFV600E-driven colorectal and melanoma cells, and reduced tumor growth in xenografts. Mechanistically, SFPQ loss in BRAF-mutant cancer cells triggered the Chk1-dependent replication checkpoint, resulting in replication stress in the absence of overt DNA damage. Affected cells stalled in S-Phase with hallmark signs of impaired replication factories. Induction of BRAFV600E and concomitant loss of SFPQ sensitized cells to a combination of DNA replication checkpoint inhibitors and chemically induced replication stress, pointing towards future therapeutic approaches exploiting nuclear vulnerabilities induced by BRAFV600E.

2020-04-27 | GSE149370 | GEO

SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells I

2019-12-31 | GSE116631 | GEO

SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells II

Project description:SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells II

| PRJNA628517 | ENA

SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells I

Project description:SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells I

| PRJNA479751 | ENA

SFPQ depletion is synthetically lethal with BRAFV600E in colorectal cancer cells

Project description:This SuperSeries is composed of the SubSeries listed below.

2020-04-27 | GSE149371 | GEO

SFPQ interacted proteins in HEK293T nucleus and cytoplasm

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

Microarray of zebrafish (Danio rerio) sfpq-/-;Tg(mnx1:GFP) against sfpq+/+;Tg(mnx1:GFP) and sfpq+/-;Tg(mnx1:GFP) siblings at 24 hpf

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

SFPQ promotes an oncogenic transcriptomic state in melanoma

Project description:Analysis of SFPQ interactome in primary melanocytes and melanoma cells. Results provide insight into the oncogenic reprogamming of SFPQ-RNA interactome and especially the interactions with key melanoma-associated coding transcripts.

2021-06-30 | GSE171291 | GEO

RNA-seq of sfpq-/- zebrafish embryos and siblings at 24 hpf

Project description:RNA was extracted from whole zebrafish embryos at 24 hpf to examine changes in gene expression and splicing in sfpq null mutants

2021-01-27 | E-MTAB-9113 | biostudies-arrayexpress

The RNA-binding protein SFPQ preserves long-intron splicing and regulates circRNA biogenesis

Project description:Circular RNAs (circRNAs) represent an abundant and conserved entity of non-coding RNAs, however the principles of biogenesis are currently not fully understood. To elucidate features important for circRNA production, we performed global analyses of RNA-binding proteins associating with the flanking introns of circRNAs, and we identified two factors, SFPQ and NONO, to be highly enriched with circRNAs. We observe a subclass of circRNAs, coined DALI circRNAs, with distal inverted Alu elements and long introns to be highly deregulated upon SFPQ knockdown. Moreover, SFPQ depletion leads to increased intron retention with concomitant induction of cryptic splicing prevalent for long introns causing in some cases premature transcription termination and polyadenylation. Aberrant splicing in the upstream and downstream regions of circRNA producing exons are critical for shaping the circRNAome, and specifically, we identify a conserved impact of missplicing in the immediate upstream region to drive circRNA biogenesis. Collectively, our data show that SFPQ plays an important role in maintaining intron integrity by ensuring accurate splicing of long introns, and disclose novel features governing Alu-independent circRNA production.

2020-09-09 | GSE157622 | GEO

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