SF3B1 inhibitor pladienolide B induces pyroptosis of ovarian cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE222199 | GEO | 2023/11/25
REPOSITORIES: GEO
Similar Datasets
Project description:SF3B1 inhibitor pladienolide B induces pyroptosis of ovarian cancer cells
| PRJNA918583 | ENA
Project description:Knockdown of mutant and/or wild-type SF3B1 in MEL202 cell line by Degron knock-in, followed by RNA-seq, to identify splicing events governed by mutant SF3B1. Control: parental MEL202 cell line. Experiments: mutant-SF3B1 knockdown; wildtype-SF3B1 knockdown; mutant SF3B1 knockout. Treatments: each of these four conditions plus and minus shld.
2015-03-11 | E-GEOD-66719 | biostudies-arrayexpress
Project description:Purpose: Small interfering RNA (siRNA)-mediated knockdown of SF3B2, a component of U2 snRNP subcomplex in the spliceosome, suppresses innate immune gene expression. To examine whether pladienolide B, a pre-mRNA inhibitor, phenocopies SF3BP2 knockdown, we compared the RNA-seq profiles of SF3B2-depleted and pladienolide B-treated PC3 cells. Method: Total RNAs were extracted from the cells and treated with DNase I. After RNA-seq libraries were constructed, next-generation sequencing and Differential Expressed Gene (DEG) analysis were performed. The library was sequenced on an Illumina NextSeq 6000 as paired-end 101 bp reads. The sequence reads were aligned to the GRCh38 reference genome using HISAT2 version 2.1.0, Bowtie2 2.3.5.1. All reads were assembled with StringTie software version 2.1.3b, using annotated genes from the NCBI database. Low quality transcripts are filtered. Afterwards, TMM Normalization are performed. Statistical analysis is performed using Fold Change, exactTest using edgeR per comparison pair. The significant results are selected on conditions of |fc|>=2 & exactTest raw p-value<0.05. DEG analysis was performed on 3 comparisons pairs using edgeR. The results showed 11,306 genes which satisfied |fc|>=2 & exactTest raw p-value<0.05 conditions in at least one of comparison pairs. For Enrichment test which based on Gene Ontology (GO) DB was conducted with significant gene list using g:Profiler tool. Result: Gene signatures of SF3B2-depleted cells were compared with those of control siRNA-treated cells. GO analysis of the down-regulated genes in SF3B2-depleted cells identified GO terms related with innate immunity. Next, gene signatures of pladienolide B-treated cells were compared with those of DMSO-treated cells. GO analysis of genes altered in pladienolide B-treated cells identified GO terms related with RNA splicing. However, innate immunity-related GO terms were classified statistically not significant. Conclusion: These observations indicate that SF3B2 knockdown and pladienolide B differentially affect the gene expression signature in PC3 cells.
2021-03-10 | GSE157725 | GEO
Project description:Much remains unknown concerning the mechanism by which the splicing machinery pinpoints short exons within intronic sequences and how splicing factors are directed to their pre-mRNA targets. Part of the explanation probably lies in differences in chromatin organization between exons and introns. Proteomic, co-immunoprecipitation, and sedimentation analyses described here indicated that SF3B1, an essential splicing component of the U2 snRNP complex, is strongly associated with nucleosomes. ChIP-seq and RNA-seq analyses revealed that SF3B1 is specifically bound to nucleosomes located at exonic positions. SF3B1 binding is enriched at nucleosomes positioned over short exons flanked by long introns that are also characterized by differential GC content between exons and introns. Disruption of SF3B1 binding to such nucleosomes affected the splicing of these exons similarly to inhibition of SF3B1 expression. Our findings suggest that the association of SF3B1 with nucleosomes is functionally important for splice site recognition and that SF3B1 conveys splicing-relevant information embedded in chromatin structure. MNase-seq on Input and SF3B1 pull-down, mRNA-seq on control and SF3B1 si-RNA treated cells as well as on TSA (Trichostatin A) treated and untreated cells.
2015-04-22 | E-GEOD-65644 | biostudies-arrayexpress
Project description:Using RNA-Seq, we determined changes to gene expression and splicing on inducible expression of SF3B1-WT and SF3B1-MUT (K700E) in K562 cells. Using RNA-Seq, we determined changes to gene expression and splicing on inducible expression of SF3B1-WT and SF3B1-MUT (K700E) in K562 cells.
2016-07-15 | E-GEOD-70959 | biostudies-arrayexpress
Project description:Recent studies have shown that multiple components of the mRNA splicing machinery are mutated in myelodysplastic syndrome (MDS) patients. SF3B1 is frequently mutated in refractory anemia with ringed sideroblasts (RARS)-MDS patients, however, the pathophysiological role of SF3B1 mutations has not been elucidated yet. In this study, we examined the function of Sf3b1 in murine hematopoiesis. Since Sf3b1 null homozygotes died during preimplantation development, in this study, we utilized Sf3b1 heterozygous mice showing grossly normal growth. We harvested bone marrow stem/progenitor (LSK) cells from wild type (WT) and Sf3b1+/- mice (n=4) at 20 weeks old. In addition, to exclude the possibility of indirect effect from bone marrow environment, we transplanted total bone marrow cells from WT or Sf3b1+/- (CD45.2+) mice into lethally irradiated CD45.1+ recipient mice, and then harvested (CD45.2+) LSK cells from the recipients (n=5) at 9 months-post transplantation.
2013-09-20 | E-GEOD-51038 | biostudies-arrayexpress
Project description:Pre-mRNA splicing and nuclear export are coordinated processes that ensure efficient and accurate gene expression. In recent years, disruptions in this process have been found to result in substantial gene expression aberrations, with potential contributions from SF3B1 mutations, whose mechanism remains elusive. The present study reveals that the K700E mutation in SF3B1 attenuates its interaction with THOC5, resulting in reduced mRNA binding by THOC5, and ultimately, the inhibition of mRNA nuclear export. Interestingly, overexpressing THOC5 can restore the attenuated interaction, facilitating mRNA nuclear export. Importantly, other cancer-associated SF3B1 mutations may exert a similar impact. Our research highlights the critical role of the THOC5–SF3B1 interaction in regulating mRNA nuclear export and provides valuable insights into the impact of SF3B1 mutations on this process.
2024-09-12 | GSE268355 | GEO
Project description:Knockdown of mutant and/or wild-type SF3B1 in MEL202 cell line by Degron knock-in, followed by RNA-seq, to identify splicing events governed by mutant SF3B1.
2015-03-11 | GSE66719 | GEO
Project description:Several DNA sequencing studies of chronic lymphocytic leukemia (CLL) revealed that the splicing factor SF3B1 accumulated somatic point mutations in about 10 percent of the patients. In most cases the mutations were located in the genomic regions coding for the C-terminal HEAT-repeat domain and in many cases, the mutations gave rise to specific amino acid substitutions. Here, we aimed to investigate differential usage of exons associated with the mutation K700E of SF3B1 in CLL tumuor cells. We generated RNA-Seq transcriptome data from two patients with mutations in SF3B1, two patient without mutations in SF3B1 and from healthy donors. We report interesting examples and possible consequences of the alternative exon usage in these genes. This dataset contains only the files resulting from the processing the RNA sequencing raw data. This avoids potential patient identifiability, but ensures the full reproducibility of the results described in the publication.
2013-12-27 | E-MTAB-2025 | biostudies-arrayexpress