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Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy

ABSTRACT: Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy

PROVIDER: PRJNA1024425 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26287813_1.fastq.gz	Fastqsanger.gz
	SRR26287813_2.fastq.gz	Fastqsanger.gz
	SRR26287814_1.fastq.gz	Fastqsanger.gz
	SRR26287814_2.fastq.gz	Fastqsanger.gz
	SRR26287815_1.fastq.gz	Fastqsanger.gz

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Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy

Project description:OSCC is a common cancer of the head and neck. Despite ongoing efforts, there remains a dearth of targeted drugs capable of effectively inhibiting OSCC growth. As the earliest discovered proto-oncogene in the SRSF family, targeted inhibition of SRSF1 plays an important role in tumor suppression. However, a comprehensive report on the expression, function, and mechanism of SRSF1 in OSCC has yet to be presented. This study retrospectively analyzed clinical samples from OSCC patients and discovered a significant correlation between the SRSF1 expression level and poor prognosis. In vitro experimentation demonstrated that SRSF1 knockdown inhibited OSCC growth, survival, lysosomal biogenesis and autophagy. To confirm the significance of lysosomal function and autophagy in the regulation of OSCC growth by SRSF1, cell rescue models were constructed. The aforementioned findings were subsequently validated in xenograft models. Ultimately, targeted knockdown of SRSF1 was found to significantly suppress OSCC growth by impeding lysosomal biogenesis and autophagy.

2023-12-01 | GSE244710 | GEO

Targeted down-regulation of SRSF1 exerts anti-cancer activity in OSCC through impairing lysosomal function and autophagy.

Project description:Oral squamous cell carcinoma (OSCC) is a common cancer of the head and neck. Despite ongoing efforts, there remains a dearth of targeted drugs capable of effectively inhibiting OSCC growth. As the earliest discovered proto-oncogene in the SRSF family, targeted inhibition of serine/arginine-rich splicing factor 1 (SRSF1) plays an important role in tumor suppression. However, the expression, function, and mechanism of SRSF1 in OSCC have not been comprehensively reported. This study retrospectively analyzed clinical samples from OSCC patients and discovered a significant correlation between the SRSF1 expression level and poor prognosis. In vitro experimentation demonstrated that SRSF1 knockdown inhibited OSCC growth, survival, lysosomal biogenesis and autophagy. To confirm the significance of lysosomal function and autophagy in the regulation of OSCC growth by SRSF1, cell rescue models were constructed. The aforementioned findings were subsequently validated in xenograft models. Ultimately, targeted knockdown of SRSF1 was found to significantly suppress OSCC growth by impeding lysosomal biogenesis and autophagy.

| S-EPMC10663830 | biostudies-literature

Splicing factor SRSF1 promotes breast cancer progression via regulating alternative splicing

Project description:Purpose:Intensive evidence have highlighted the effect of aberrant alternative splicing (AS) events triggered by dysregulation of SR protein family on cancer progression. Nonetheless, the underlying mechanism in breast cancer (BRCA) remains elusive. Here we sought to explore the molecular function of SRSF1 and identify the key AS events regulated by SRSF1 in BRCA. Methods:We conducted comprehensive analysis for the expression and the clinical correlation of SRSF1 in BRCA based on TCGA, Metabric database, clinical tissue samples and BRCA cell lines. Functional analysis of SRSF1 in BRCA was conducted in vitro and in vivo. SRSF1-mediated AS events and its binding motif were identified by RNA-seq, RNA immunoprecipitation-PCR (RIP-PCR) and in vivo crosslinking followed by immunoprecipitation (CLIP), which was further validated by the minigene reporter assay. Finally, the expression and their clinical significance were validated in clinical samples and TCGA database. Results:SRSF1 was upregulated in BRCA samples, associated positively with tumor grade and Ki-67 index, and correlated with poor prognosis in hormone receptor positive (HR+) cohort, which facilitated tumor progression in vitro and in vivo. We identified SRSF1-mediated AS events and discovered the SRSF1 binding motif in the regulation of PTPMT1. Furthermore, PTPMT1 splice switching regulated by SRSF1 partially mediated the oncogenic role of SRSF1 via the AKT/C-MYC axis. Additionally, PTPMT1 splice switching was validated in tissue samples of BRCA patients. Conclusions:Collectively, SRSF1 exerts the oncogenic roles in BRCA partially through regulating AS of PTPMT1, which could be a candidate prognostic factor and therapeutic target in HR+ BRCA cohort.

2021-05-25 | GSE163025 | GEO

Chip-chip from Mouse MEFs cells for H3K36me3, Srsf1, Psip1(A300-847 antibody).

Project description:The p52 isoform of Psip1/Ledgf links histone H3K36 methylation and the regulation of alternative splicing. Chromatin immunoprecipitation (ChIP) of Psip1 together with H3K36me3 and Srsf1 and by ChIP-on-chip analysis demonstrated that H3K36me3, Psip1 and SRSF1 enrichment correlates on the gene bodies Array design includes 2 dye swap replicates for Srsf1 and Psip1-/- samples, and single arrays for PSIP and H3K36me3 samples

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Next Generation Sequencing Analysis of SRSF1 flox/flox and SRSF1-KO pancreatic islet Transcriptome

Project description:we report insulin secretion defects in SRSF1 Ins2-Cre mice, in which SRSF1 is ablated in pancreatic β cells.

2023-04-17 | GSE173455 | GEO

SRSF1 HITS-CLIP

Project description:SRSF1 HITS-CLIP

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SRSF1 HITS-CLIP in MDA-LM2

Project description:To identify SRSF1 binding sites on RNAs, we performed HITS-CLIP of endogenous SRSF1 in MDA-LM2 cells

2019-12-26 | GSE131745 | GEO

SRSF1 HITS-CLIP

Project description:To identify METTL3 binding sites on RNAs, we performed HITS-CLIP of endogenous SRSF1

2019-12-26 | GSE130867 | GEO

SRSF1 role in cellular gene expression and splicing

Project description:SRSF1 is an abundant RNA-binding protein with functions in mRNA splicing, stability, translation and transcription of cellular and viral genes. We analyzed the role that SRSF1 plays in cellular gene transcription and splicing by transfecting HEK293 cells with a SRSF1 expression plasmid and by analyzing the transcriptome of the transiently transfected cells 15 hrs and 48 hrs post transfection. We also explored the role of the SRSF1 domains by transfecting a deletion clone of SRSF1 carrying only the RNA Recognition Motifs 1 and 2 (RRM1,2) but not the Arg-Ser rich (SR) domain.

2019-03-20 | GSE124397 | GEO

Total RNA-seq of siRNA-mediated SRSF1 knockdown

Project description:To identify changes in splicing patterns following SRSF1 knockdown, RNA-sequencing was performed on breast cancer cells transfected with siRNAs targeting SRSF1.

2019-12-26 | GSE130868 | GEO

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