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Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner (ONT long read sequencing)

ABSTRACT: Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner (ONT long read sequencing)

PROVIDER: PRJNA1081609 | ENA |

REPOSITORIES: ENA

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Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner

Project description:Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner

| PRJNA1081333 | ENA

Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner (Illumina short read)

Project description:Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner (Illumina short read)

| PRJNA1071137 | ENA

Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner (ONT long read sequencing)

Project description:The Cdc2-like kinase (CLK)-family is a regulator of the splicing process. Here, we report the effect of Lorecivivint (SM04690), a CLK/DYRK inhibitor, on alternative splicing in the prostate cancer cell line 22Rv1. Lorecivivint treatment lead to impaired growth and disruption of several oncogenic pathways, including the androgen response, MYC, and Wnt/β-catenin hallmark pathways. Taken together, this data shows that alternative splicing is a pivotal process in prostate cancer and is suitable to be targeted.

2024-09-26 | GSE259334 | GEO

Proteins that interact with CLK2 (WT) or CLK2 (T343A)

Project description:Our results show that CLK2 undergoes liquid-liquid phase separation (LLPS) in response to heat shock stress. Phosphorylation of CLK2 at T343 prevents the LLPS of CLK2. To identify the proteins that recruited to the CLK2 condensates, we immunoprecipitated CLK2 (WT) or (T343A) proteins with FLAG antibody and performed mass spectrometry to detect the interacting proteins.

2023-11-06 | PXD040997 | Pride

Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner

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

2024-09-26 | GSE259335 | GEO

ARv7 represses tumor suppressors genes in castration-resistant prostate cancer [RNA-Seq]

Project description:Endocrine therapies in prostate cancer (PCa) treatment block androgen receptor (AR) function, but are palliative as tumors progress to a lethal, castration-resistant state (CRPC). CRPC remains dependent on AR signaling, which can act through the full-length AR (ARfl) or constitutively active splice variants, e.g. ARv7. We show here that both ARfl and ARv7 bind to the same genomic region and heterodimerize in a CRPC cell line model, but regulate distinct transcriptomes. ARv7, unlike ARfl, preferentially represses transcription and demonstrates an increased affinity for co-repressors, decreased chromatin residence time and lower dependence on FOXA1 binding. We identified a group of ARv7-repressed genes, including the UDP-galactosyltransferase B4GALT1 that are down-regulated during PCa progression and important for CRPC growth. In conclusion, we propose that ARv7 acts as a transcriptional repressor of genes that limit proliferation, a function that should be targeted in CRPC patients.

2018-11-02 | GSE106560 | GEO

ARv7 represses tumor suppressors genes in castration-resistant prostate cancer [ChIP-Seq]

2018-11-02 | GSE106559 | GEO

Effect of CLK2 overexpression on alternative splicing

Project description:To investigate the function CLK2 in the regulation of alternative splicing, we established HeLa cells overexpressing GFP, CLK2 (WT), or (T343A). We then performed alternative splicing analysis using data obtained from RNA-seq of the three cell lines.

2023-11-09 | GSE227673 | GEO

Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner (Illumina short read)

2024-09-26 | GSE254611 | GEO

Effect of CLK2 expression in the regulation of intron retention during heat shock [RNA-seq]

Project description:Intron retention (IR) constitutes a less explored form of alternative splicing, wherein introns are retained within mature mRNA transcripts. Our investigation demonstrates that the CDC-like kinase 2 (CLK2) undergoes liquid-liquid phase separation (LLPS) within nuclear speckles in response to heat shock (HS). The formation of CLK2 condensates depends on the intrinsically disordered region (IDR) located within the N-terminal amino acids 1-148. Phosphorylation at residue T343 sustains CLK2 kinase activity and facilitates autophosphorylation, thus inhibiting the LLPS activity of the IDR. These CLK2 condensates initiate the reorganization of nuclear speckles, transforming them into larger, rounded structures. Moreover, these condensates facilitate the recruitment of splicing factors into these compartments, potentially restricting their access to mRNA for intron splicing. Consequently, the formation of CLK2 condensates promotes the IR.

2024-07-15 | GSE271918 | GEO

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