CircCDYL association with hnRNPL modulates CDYL isoform switching in Breast Cancer cells
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA1252746 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR33214213_1.fastq.gz | Fastqsanger.gz | |||
| SRR33214213_2.fastq.gz | Fastqsanger.gz | |||
| SRR33214214_1.fastq.gz | Fastqsanger.gz | |||
| SRR33214214_2.fastq.gz | Fastqsanger.gz | |||
| SRR33214215_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 24 |
Similar Datasets
Project description:Circular RNAs (circRNAs) are covalently closed transcripts involved in the regulation of different cellular processes, and their dysregulation has been frequently observed in cancer. In this study, we investigated the role of circCDYL, a circRNA generated from the CDYL gene, in modulating alternative splicing (AS) and isoform switching in breast cancer cells. Analysis of circRNA profiles in breast cancer cells showed that circCDYL expression increased in estrogen receptor alpha (ERα)-downregulated cells, suggesting a potential link between circCDYL-mediated regulation and ERα signaling pathways. RNA-Sequencing analysis following circCDYL knock-down in MCF-7 cells revealed significant alterations in the splicing pattern, with over 2,900 splicing events significantly affected. Through RNA immunoprecipitation and RNA pull-down assays, we found evidence of an association between circCDYL and the splicing factor hnRNPL. To explore the consequences of this association, we performed AS and isoform switching analysis after circCDYL and hnRNPL silencing, revealing significant effects on AS and a weaker modulation of isoform switching events. Furthermore, we observed that circCDYL and hnRNPL modulated CDYL isoform expression, as confirmed by isoform-specific qRT-PCR analysis. Chromatin immunoprecipitation assays also indicated changes in chromatin marks at the CDYL locus upon knock-down of circCDYL and hnRNPL. These results suggested a possible association between circCDYL and hnRNPL, which contributed to the regulation of alternative splicing in breast cancer cells and may be involved in the modulation of isoform expression and chromatin dynamics of CDYL gene.
2025-04-18 | GSE295065 | GEO
Project description:In the current project with aim to unequivocally characterize a novel splicing-regulatory network that proves to be a central mediator of endothelial barrier function and vascular integrity. At the core of this network is the endothelial enriched lncRNA NTRAS (annotated as RP11-354k1.1) is shown to control alternative splicing decisions in HUVECs through interplaying with splicing factor hnRNPL. Specifically, in the project we show that NTRAS sequesters the splicing factor hnRNPL through a CA dinucleotide motif, to enhance TJP1 exon 20 usage, thereby TJP1α+ isoform. In turn disrupting TJP1α+ isoform expression impaired endothelial barrier function. Collectively, this splicing-regulatory network might prove fundamental in unlocking new interventions strategic to prevent or reverse vascular leakage.
2022-01-10 | E-MTAB-11311 | biostudies-arrayexpress
Project description:Isoform switching events in esophageal adenocarcinoma progression
| PRJNA798444 | ENA
Project description:Global isoform switching in esophageal adenocarcinoma (EAC) or precursor lesions has not been previously characterized. This form of alternative splicing has recently been recognized as highly prevalent in multiple other cancers. In this study, isoform switch analysis was performed using next generation sequencing of RNA isolated from patient tissues across a histopathological continuum, ranging from low risk Barrett’s esophagus (BE) to BE with advanced dysplasia. Patients were stratified based on esophageal tissue histopathology.
2022-08-17 | GSE193946 | GEO
Project description:Here we report that the epigenetic factor Chromodomain Y-like (CDYL) protein is a critical regulator for the initiation and maintenance of activity-dependent intrinsic neuroplasticity. Genome-wide ChIP-sequencing analysis revealed that CDYL regulates multiple neuronal functional pathways including voltage-gated ion channels in mouse brains. We showed that CDYL binds to a regulatory element in the intron region of SCN8A and mainly recruits H3K27me3 activity for transcriptional repression of the gene. Injection of lentivirally-delivered CDYL shRNA to rat hippocampal neurons resulted in augmented Nav1.6-mediated sodium currents, lower neuronal threshold and increased seizure susceptibility, whereas transgenic mice over-expressing CDYL had higher neuronal threshold and were less prone to epileptogenesis. Finally, examination of human brain tissues revealed decreased expression of CDYL and increased expression of SCN8A in the temporal lobe epilepsy group. Together, our findings indicate CDYL is a critical player for experience-dependent gene regulation in controlling intrinsic excitability, which potentially contributes to learning and memory and CNS disorders involving change in activity such as epilepsy.
2017-06-25 | GSE96721 | GEO
Project description:Characterization of splice isoform switching during human kidney development
| PRJNA633147 | ENA
Project description:The multifunctional RNA-binding protein hnRNPL has been implicated in antibody class switching but its broader function in B cells is unknown. Here, we show that hnRNPL is essential for B cell activation, and thereby germinal center and antibody responses. Upon activation, hnRNPL-deficient B cells show proliferation defects and increased apoptosis. The comparative analysis of RNA-seq data from B cells and another 8 hnRNPL-depleted cell types reveals a common function in the Myc and E2F transcriptional programs required for proliferation, likely borne out of a large alternative splicing change affecting multiple transcription regulators. Notably, while individual gene expression changes were cell type specific, several alternative splicing events affecting histone modifiers like SIRT1, KDM6A, and NSD2, were conserved across cell types, which could contribute to gene expression changes upon hnRNPL loss. SIRT1 reduction due to alternative splicing, and other transcriptional changes suggested mitochondrial defects in hnRNPL-deficient B cells. We confirmed dysfunctional mitochondria and ROS overproduction, which could explain the B cell activation defect. Thus, hnRNPL is essential for the resting to activated B cell transition by regulating transcriptional programs, most likely by splicing regulation affecting several histone modifiers.
2024-04-24 | GSE242069 | GEO
Project description:We report that the epigenetic factor CDYL is crucial for pain processing. CDYL downstreams in mouse dorsal root ganglia (DRG) are mostly associated with neurological functions, including chemical synaptic transmission, regulation of membrane potential and ion transport. CDYL facilitates H3K27me3 deposition at the Kcnb1 intron region thus silencing Kv2.1 transcription. Loss function of CDYL enhances total Kv and Kv2.1 current density in DRG and knockdown of Kv2.1 reverses the pain-related phenotypes of Cdyl deficiency mice.
2022-02-08 | GSE190751 | GEO
Project description:Impaired endometrial receptivity is one of the major causes of recurrent implantation failure (RIF), and the underlying molecular mechanism has not been fully elucidated. We demonstrated that Chromodomain Y like (CDYL) was highly expressed in the endometrium at mid-secretory phase during the normal menstrual cycles. However, the expression of CDYL was down-regulated in the endometrial tissues obtained from women with RIF, consistently with the protein level of LIF, which is the marker of endometrial receptivity. Knockdown of CDYL significantly decreased the cell migration of human endometrial Ishikawa cells and primary endometrial cells. Genomic analyses revealed that CDYL gene silencing resulted in decreased expression of many genes associated with cytoskeleton and migration regulation.
2020-09-28 | GSE141239 | GEO
Project description:Ovarian cancer has the highest mortality rate among gynecologic tumors worldwide, with unclear underlying mechanisms of pathogenesis. RNA-binding proteins (RBPs) primarily direct post-transcriptional regulation through modulating RNA metabolism. Recent evidence demonstrates that RBPs are also implicated in transcriptional control. However, the role and mechanism of RBP-mediated transcriptional regulation in tumorigenesis remain largely unexplored. Here, we show that the RBP heterogeneous ribonucleoprotein L (hnRNPL) interacts with chromatin and regulates gene transcription by forming phase-separated condensates in ovarian cancer. hnRNPL phase separation activates PIK3CB transcription and glycolysis, thus promoting ovarian cancer progression. Notably, we observe that the PIK3CB promoter is transcribed to produce a non-coding RNA which interacts with hnRNPL and promotes hnRNPL condensation. Furthermore, hnRNPL is significantly amplified in ovarian cancer, and its high expression predicts poor prognosis for ovarian cancer patients. By using cell-derived xenograft and patient-derived organoid models, we show that hnRNPL knockdown suppresses ovarian tumorigenesis. Together, our study reveals that phase separation of the chromatin-associated RBP hnRNPL promotes PIK3CB transcription and glycolysis to facilitate tumorigenesis in ovarian cancer. The formed hnRNPL-PIK3CB-AKT axis depending on phase separation can serve as a potential therapeutic target for ovarian cancer.
2025-02-14 | GSE289102 | GEO