RBM25 depletion suppresses colon cancer progression through regulating alternative splicing of MNK2
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE245341 | GEO | 2025/06/21
REPOSITORIES: GEO
Similar Datasets
Project description:RBM25 depletion suppresses colon cancer progression through regulating alternative splicing of MNK2
| PRJNA1027849 | ENA
Project description:Cancer sequencing studies have implicated regulators of pre-mRNA splicing as important disease determinants in Acute Myeloid Leukemia (AML), but the underlying mechanisms have remained elusive. We hypothesized that “non-mutated” splicing regulators may also play a role in AML biology and therefore conducted an in vivo shRNA screen in a mouse model of CEBPA mutant AML. This led to the identification of the splicing regulator RBM25 as a novel tumor suppressor, and down-regulation of RBM25 increased proliferation and decreased apoptosis in human leukemic cell lines. Mechanistically, we could show that RBM25 controlled the splicing of key genes, including those encoding the apoptotic regulator BCL-x and the MYC inhibitor BIN1. Specifically, we demonstrated that RBM25 acts as a regulator of MYC activity and sensitizes cells to increased MYC levels. This mechanism also appears to be operative in human AML patients where RBM25 levels correlative inversely with MYC activity and clinical outcome.
2018-12-07 | GSE114027 | GEO
Project description:The goal of this study was to determine the role of RBM25 in pre-mRNA splicing and examine whether lysine 77 contributes to this function.
2016-10-26 | GSE89140 | GEO
Project description:Alternative splicing (AS) enables genes to be translated into a vast diversity of proteins while aberrant AS predisposes cells to abnormal biological processes. As is closely associated with AS, RNA binding proteins (RBPs) are gradually gaining attention. RBM 25 was reported to participate in the cardiac pathophysiological process via AS regulation. Nonetheless, gaps still existed in whether RBM 25 functions in heart failure by its splicing factor role. H9C2 cells with excessively expressed RBM25 were used to filtrate different expression genes (DEGs) and analyze for RBM25-regulated AS by RNA-seq. Next, iRIP-seq was performed to examine its binding targets. For genes screened, further RT-qPCR-based validation was conducted. RBM25 overexpression caused expressive alteration in 80 genes mainly involved in the inflammatory response and virus response. Notably, RBM25 partially modulated AS of differential genes enriched in the apoptotic process and bound to genes clustered at inflammation response. Further, qRT-PCR verified Slc38a9, IL-17RC, Csf1, and Coro6 as targets of RBM25 being bound to and AS-regulated. Herein, our work demonstrated that by exerting its binding capability, RBM25 may serve as a regulator of related RNA expressive levels and AS process to confer negative impacts on cardiac inflammation in cardiomyocytes. Our study provided preliminary evidence regarding the understanding of RBM25 in heart failure complicated by inflammation.
2023-10-05 | GSE209940 | GEO
Project description:Alternative splicing (AS) enables genes to be translated into a vast diversity of proteins while aberrant AS predisposes cells to abnormal biological processes. As is closely associated with AS, RNA binding proteins (RBPs) are gradually gaining attention. RBM 25 was reported to participate in the cardiac pathophysiological process via AS regulation. Nonetheless, gaps still existed in whether RBM 25 functions in heart failure by its splicing factor role. H9C2 cells with excessively expressed RBM25 were used to filtrate different expression genes (DEGs) and analyze for RBM25-regulated AS by RNA-seq. Next, iRIP-seq was performed to examine its binding targets. For genes screened, further RT-qPCR-based validation was conducted. RBM25 overexpression caused expressive alteration in 80 genes mainly involved in the inflammatory response and virus response. Notably, RBM25 partially modulated AS of differential genes enriched in the apoptotic process and bound to genes clustered at inflammation response. Further, qRT-PCR verified Slc38a9, IL-17RC, Csf1, and Coro6 as targets of RBM25 being bound to and AS-regulated.
2023-10-05 | GSE209941 | GEO
Project description:Efficient targeted control of exon splicing is a major goal of functional genomic and therapeutic applications. Guide RNA-directed, deactivated (d)Cas CRISPR enzymes fused to splicing effectors represent a promising strategy due to the flexibility and presumed specificity of these systems. However, efficient, selective, and generalizable activation of targeted endogenous exons using this approach has not been reported. Here, we identify dCasRx-RBM25 as a potent activator of exons by screening over 300 dCasRx splicing factor fusions tethered to splicing reporters. dCasRx-RBM25 also strongly activates splicing of endogenous alternative exons, when recruited to downstream intron sequences using single guide RNAs. In transcriptome wide analyses we observe a high degree of specificity of dCasRx-RBM25 for endogenous exon targeting. We further leverage the guide array-processing activity of dCasRx to simultaneously target multiple endogenous exons for activation and repression by dCasRx-RBM25. Our results pave the way for versatile exon-resolution functional assays and splicing-directed therapeutic applications.
2024-09-19 | GSE243979 | GEO
Project description:We used RNA-seq platform to determine role of a splicing factor RBM25 in regulation of gene expression and pre-mRNA splicing. We found that a loss-of-function allele of RBM25, rbm25-1, causes up- and down-regulation of a large number of genes. We further found that the rbm25-1 mutation results in defects in altenative splicing of transcripts of many genes including signal transduction components in stress responses. Examination of mRNA levels in bulked individual wild type and rbm25-1 mutant seedlings before and after ABA treatment.
2015-10-28 | E-GEOD-66737 | biostudies-arrayexpress
Project description:RNA-binding motif protein 25 (RBM25) is a poorly characterized RNA-binding protein that is involved in several biological processes and regulates the proliferation and metastasis of tumor cells. The regulatory role of RBM25 in hepatocellular carcinoma (HCC) is unknown. Here, RBM25 expression and outcomes in HCC patients were evaluated using The Cancer Genome Atlas database. RBM25 was overexpressed in HCC patients compared with the healthy group. The high expression of RBM25 in tumor tissues was significantly related to poor overall survival (P<0.001). Overexpression of RBM25 significantly contributed to poorer survival in male patients and N0 stage patients (P<0.001). Spearman analysis and weighted gene co-expression network analysis identified 694 RBM25-related genes. Protein-protein interaction network analysis revealed the Cluster with the highest score, which positively correlated with RBM25. CDCA5 and INCENP were identified as the core functional genes related to RBM25. The overexpression of CDCA5 and INCENP in HCC patients was examined using the Human Protein Atlas database. The findings collectively indicated that RBM25 may interact with CDCA5 and INCENP to regulate HCC. Our detailed characterization of RBM25 protein interactions and related core functional genes provides a basis for further studies aimed at identifying molecular regulatory pathways or splicing events.
| S-EPMC8806338 | biostudies-literature
Project description:MethodsFirst, the expression of LGR4 in HCC tumor tissues and cell lines was detected by western blotting and immunofluorescence. The ability of cell proliferation, migration, and invasion was detected with CCK8, wound-healing, and transwell assays when overexpressing LGR4 or treating with metformin. The β-catenin expression was detected by immunofluorescence. In order to investigate novel AS-associated LGR4, we discarded LGR4 isoforms from GSO databases. We used siRNA to knock down the specific isoform to check the cell proliferation, migration, and invasion when treated with metformin.ResultsThe level of LGR4 expression was higher in HCC cell lines and tumor tissues. The HCC cell proliferation, migration, and invasion were increased when overexpressing LGR4, which could be reduced by metformin treatment. The GEO database (GSE190076) showed that LGR4 had switching properties in HCC cell lines treated with metformin. We used siRNA to knock down the specific isoform, and the result showed that the specific isoform siRNA could promote the inhibition of cell invasion caused by metformin treatment.ConclusionsLGR4 could promote the ability of cell proliferation, migration, and invasion in HCC, which could be reduced by metformin through alternative splicing.
| S-EPMC9652085 | biostudies-literature
Project description:Talaromyces marneffei (T. marneffei) immune escape is essential in the pathogenesis of talaromycosis. It is currently known that T. marneffei achieves immune escape through various strategies. However, the role of cellular alternative splicing (AS) in immune escape remains unclear. Here, we depict the AS landscape in macrophages upon T. marneffei infection via high-throughput RNA sequencing and detect a truncated protein of NCOR2 / SMRT, named NCOR2-013, which is significantly upregulated after T. marneffei infection. Mechanistic analysis indicates that NCOR2-013 forms a co-repression complex with TBL1XR1 / TBLR1 and HDAC3, thereby inhibiting JunB-mediated transcriptional activation of pro-inflammatory cytokines via the inhibition of histone acetylation. Furthermore, we identify TUT1 as the AS regulator that regulates NCOR2-013 production and promotes T. marneffei immune evasion. Collectively, these findings indicate that T. marneffei escapes macrophage killing through TUT1-mediated alternative splicing of NCOR2 / SMRT, providing insight into the molecular mechanisms of T. marneffei immune evasion and potential targets for talaromycosis therapy.
| S-EPMC10579421 | biostudies-literature