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Splicing factor SRSF1 promotes breast cancer progression via regulating alternative splicing

ABSTRACT: Splicing factor SRSF1 promotes breast cancer progression via regulating alternative splicing

PROVIDER: PRJNA684349 | ENA |

REPOSITORIES: ENA

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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

SRSF1-mediated alternative splicing is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition [LACE-seq]

Project description:Alternative splicing (AS) plays significant roles in fundamental biological activities. AS also are prevalent in the testis, but the regulations of alternative splicing in spermatogenesis is vague. Here, we report that Serine/arginine-rich splicing factor 1 (SRSF1), plays critical roles in alternative splicing and male reproduction. Male germ cell-specific deletion of Srsf1 led to complete infertility and abnormal spermatogenesis. We further demonstrated that Srsf1 is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition. Mechanistically, by combining RNA-seq data with LACE-seq data, we showed that SRSF1 regulatory networks have functions in spermatogenesis. Particularly, we found that SRSF1 affects the AS of Stra8 in a direct manner and Dazl, Dmc1, Mre11a, Syce2 and Rif1 in an indirect manner. Taken together, our findings demonstrate that SRSF1 has crucial functions in spermatogenesis and male fertility by regulating alternative splicing.

2024-03-31 | GSE226551 | GEO

SRSF1-mediated alternative splicing is required for spermatogonial stem cell differentiation and mitotic-to-meiotic transition [RNA-Seq]

2024-03-31 | GSE226550 | GEO

SRSF1 is involved in alternative mRNA splicing in granulosa cell survival

Project description:Granulosa cells abnormalities are one of the characteristics of premature ovarian insufficiency (POI). Abnormal expression of serine/arginine-rich splicing factor 1 (SRSF1) can causes a variety of diseases, but the role of SRSF1 in mouse granulosa cells has been poorly reported. In this study, we found that SRSF1 was expressed in the nuclei of both mouse oocytes and granulosa cells. Specific knockout of SRSF1 in granulosa cells was performed using Foxl2-creERT2 mice, and morphological staining showed that follicular development was blocked. In addition, granulosa cell proliferation decreased and cell apoptosis increased. The differential gene Gene Ontology (GO) analysis of RNA-Seq results showed abnormal expression of DNA repair, cell killing and other signaling pathways. Alternative splicing (AS) analysis showed that SRSF1 affected DNA damage in granulosa cells by regulating genes related to DNA repair. In conclusion, SRSF1 in granulosa cells affects female reproduction by controlling the development of follicles through regulating granulosa cell DNA repair related genes.

2024-01-01 | GSE228975 | GEO

Identification of alternative splicing events regulated by the splicing factor SRSF1 using data from exon-junction microarray technologies

Project description:Analysis to identify genome-wide differential alternative splicing events in A549 cells in which the levels of the gene SRSF1 were down-regulated with a specific siRNA 9 samples from three independent experiments using A549 cells transfected with lipofectamine alone, scramble siRNA or SRSF1 siRNA

2013-12-18 | E-GEOD-53410 | biostudies-arrayexpress

SRSF1 governs progenitor-specific alternative splicing to maintain adult epithelial tissue homeostasis and renewal

Project description:Alternative splicing generates distinct mRNA variants and is essential for development, homeostasis, and renewal. Proteins of the serine/arginine (SR)-rich splicing factor family are major splicing regulators that are broadly required for organ development as well as cell and organism viability. However, how these proteins support adult organ function remains largely unknown. Here, we used the continuously growing mouse incisor as a model to dissect the functions of the prototypical SR-family protein SRSF1 during tissue homeostasis and renewal. We identified an SRSF1-governed alternative splicing network that is specifically required for dental proliferation and survival of progenitors but dispensable for the viability of differentiated cells. We also observed a similar progenitor-specific role of SRSF1 in the small intestinal epithelium, indicating a conserved function of SRSF1 across adult epithelial tissues. Thus, our findings define a regulatory mechanism by which SRSF1 specifically controls progenitor-specific alternative splicing events to support adult tissue homeostasis and renewal.

2022-01-18 | GSE193492 | GEO

Splicing Factor SRSF1 Promotes Tumorigenesis via Oncogenic Splice-Switching and Predicts Poor Prognosis in Multiple Myeloma

Project description:Alternative splicing (AS) and its regulation play critical roles in cancer, yet the dysregulation of AS and its molecular bases in multiple myeloma (MM) development have not yet been elucidated. We identified SRSF1 as a key splicing factor in tumor progression, SRSF1 expression was frequently upregulated in MM and correlated with poor survival.We conducted transcriptome comparison of SRSF1-knockdown and control cells highlighted the functional importance of SRSF1 in mediating MM progression through regulating AS, and revealed the upstream and downstream molecular regulation mechanism of SRSF1. Further investigation to clarify molecular mechanisms and to replicate our findings is necessary. Thus, our findings are of high translational relevance and are expected to have a substantial impact on the development of a promising epigenetic approach for investigating targeted therapies for MM with high SRSF1 expression.

2022-09-04 | GSE160724 | GEO

The splicing factor SRSF1 regulates the radio-resistance of cancer cells through modulating the alternative splicing of PTPMT1

Project description:RNA-seq was performed on H1299 cells that stably knocking down SRSF1 or control, as well as these cells that were treated with ionizing radiation, in order to profile the alternative splicing events that were regulated by SRSF1 upon ionizing radiation.

2018-11-12 | GSE107224 | GEO

Identification of alternative splicing events regulated by the splicing factor SRSF1 using data from exon-junction microarray technologies

Project description:Analysis to identify genome-wide differential alternative splicing events in A549 cells in which the levels of the gene SRSF1 were down-regulated with a specific siRNA

2013-12-18 | GSE53410 | GEO

Identification of alternative splicing changes upon ablation of cytoplasmic SRSF1.

Project description:SRSF1, shuttles between the nucleus and cytoplasm affecting post-splicing processes. However, the physiological significance of this remains unclear. Here, we used genome editing to knock-in a nuclear retention signal (NRS) in Srsf1 to create a mouse model harboring a non-shuttling SRSF1 protein. We then assessed whether alblation of shuttling activities of SRSF1 affects its nuclear functions.

2021-08-05 | GSE157269 | GEO

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