Targeting the splicing factor SRSF10 in mouse HCC tumors shapes tumor immunity and immunotherapy
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ABSTRACT:
PROVIDER: PRJNA1140105 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR29984115_1.fastq.gz | Fastqsanger.gz | |||
| SRR29984115_2.fastq.gz | Fastqsanger.gz | |||
| SRR29984116_1.fastq.gz | Fastqsanger.gz | |||
| SRR29984116_2.fastq.gz | Fastqsanger.gz |
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Project description:The efficacy of immune checkpoint blockade (ICB) therapy in hepatocellular carcinoma (HCC) patients remains poor. This article aims to uncover the role and mechanism of SRSF10 in HCC immunotherapy. SRSF10 is upregulated in a variety of tumors and is associated with poor prognosis. SRSF10 binds to the 3’UTR region of MYB and enhances the stability of MYB RNA levels. This activation leads to increased transcriptional expression of key enzymes associated with glycolysis, such as GLUT1, HK1, and LDHA, resulting in higher lactate content in tumor cells. The lactate in tumor cells inside can increase histone lactylation so as to upregulated the expression of SRSF10. Besides, the lactate produced by tumors promotes lactylation of the histone H3K18la site upon transport into macrophages, which could activate transcription of M2 macrophage genes and increase protumour macrophage activity, so as to creating a suppressive immune microenvironment. Clinically, SRSF10 can be utilized as a biomarker to assess the resistance to immunotherapy in different types of solid tumors. The pharmacological targeting of SRSF10 with 1C8 has been shown to be effective in both murine and human preclinical models. In conclusion, we prove that the SRSF10/MYB/glycolysis/lactate axis is critical for triggering immune evasion and anti-PD-1 resistance.
2024-08-18 | GSE273080 | GEO
Project description:We investigated the impact of SRSF10 knockdown on transcriptome in HCC cells through RNA-seq assays
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Project description:Splicing factor SRSF10 is known to function as a sequence-specific splicing activator. Here, we used RNA-seq coupled with bioinformatics analysis to identify the extensive splicing network regulated by SRSF10 in chicken cells. We found that SRSF10 promoted both exon inclusion and exclusion. Functionally, many of SRSF10-verified alternative exons are linked to pathways of stress and apoptosis. Importantly, reconstituted SRSF10 in knockout cells recovered wild-type splicing patterns and considerably rescued the stress-related defects. Together, our results provide mechanistic insight into SRSF10-regulated alternative splicing events in vivo and demonstrate that SRSF10 plays a crucial role in cell survival under stress conditions. RNA-seq for wide type (WT) and SRSF10-deficient (KO) chicken DT40 cells
2014-01-22 | E-GEOD-53354 | biostudies-arrayexpress
Project description:During adipocyte differentiation, significant alternative splicing changes occur in association with the adipogenic process. However, little is known about roles played by splicing factors in this process. We observed that mice deficient for the splicing factor SRSF10 exhibit severely impaired development of subcutaneous white adipose tissue as a result of defects in adipogenic differentiation. To identify splicing events responsible for this, RNA-seq analysis was performed using embryonic fibroblast cells. Several SRSF10-affected splicing events that are implicated in adipogenesis have been identified. Skipping of lipin1 exon 7 is controlled by SRSF10-regulated cis-element located in the constitutive exon 8. The activity of this element depends on the binding of SRSF10 and correlates with the relative abundance of lipin1a mRNA. A series of experiments demonstrated that SRSF10 controls the production of lipin1a and thus promotes adipocyte differentiation. Indeed, lipin1a expression could rescue SRSF10-mediated adipogenic defects. Taken together, our results identify SRSF10 as an essential regulator for adipocyte differentiation and also provide new insights into splicing control by SRSF10 in lipin1 pre-mRNA splicing. RNA-seq for wide type (WT) and SRSF10-deficient (KO) mouse MEF cells
2014-05-12 | E-GEOD-54226 | biostudies-arrayexpress
Project description:MYC-HCC treated with immunotherapy
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Project description:Splicing factor SRSF10 is known to function as a sequence-specific splicing activator. Here, we used RNA-seq coupled with bioinformatics analysis to identify the extensive splicing network regulated by SRSF10 in chicken cells. We found that SRSF10 promoted both exon inclusion and exclusion. Functionally, many of SRSF10-verified alternative exons are linked to pathways of stress and apoptosis. Importantly, reconstituted SRSF10 in knockout cells recovered wild-type splicing patterns and considerably rescued the stress-related defects. Together, our results provide mechanistic insight into SRSF10-regulated alternative splicing events in vivo and demonstrate that SRSF10 plays a crucial role in cell survival under stress conditions.
2014-01-22 | GSE53354 | GEO
Project description:During adipocyte differentiation, significant alternative splicing changes occur in association with the adipogenic process. However, little is known about roles played by splicing factors in this process. We observed that mice deficient for the splicing factor SRSF10 exhibit severely impaired development of subcutaneous white adipose tissue as a result of defects in adipogenic differentiation. To identify splicing events responsible for this, RNA-seq analysis was performed using embryonic fibroblast cells. Several SRSF10-affected splicing events that are implicated in adipogenesis have been identified. Skipping of lipin1 exon 7 is controlled by SRSF10-regulated cis-element located in the constitutive exon 8. The activity of this element depends on the binding of SRSF10 and correlates with the relative abundance of lipin1a mRNA. A series of experiments demonstrated that SRSF10 controls the production of lipin1a and thus promotes adipocyte differentiation. Indeed, lipin1a expression could rescue SRSF10-mediated adipogenic defects. Taken together, our results identify SRSF10 as an essential regulator for adipocyte differentiation and also provide new insights into splicing control by SRSF10 in lipin1 pre-mRNA splicing.
2014-05-12 | GSE54226 | GEO
Project description:The regulation of transcriptome in HCC cells by SRSF10 [Huh7_shSRSF10_RNAseq]
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Project description:Alternative splicing expands the proteome complexity and plays essential roles in tissue development and human diseases. However, how spermatogenesis is regulated by alternative splicing remains largely unknown. Here, using germ cell-specific knockout mouse model, we demonstrate that the splicing factor Srsf10 is essential for spermatogenesis and male fertility. Depletion of Srsf10 in germ cells had little effect on the formation of SSCs but impeded the expansion of progenitor spermatogonia, leading to the failure of spermatogonia differentiation and meiosis initiation. This was evidenced by the decreased expression of progenitor cell markers in bulk RNA-seq, and much less progenitor and differentiating spermatogonia in single-cell RNA-seq data. Furthermore, the expression of genes involved in cell cycle was abnormal in all subtypes of spermatogonia identified in single-cell RNA-seq data. Notably, using isolated spermatogonia, we found that Srsf10 depletion disturbed the alternative splicing of hundreds of genes, which were preferentially associated with cell cycle, mitotic cell cycle checkpoint and germ cell development, including Dazl, Kit, Ret, Sycp1, Nasp and Bora. These data suggest that SRSF10 is critical for the expansion of progenitor spermatogonia by regulating alternative splicing, expanding our understanding of the novel mechanism underlying spermatogenesis.
2022-11-07 | GSE190646 | GEO
Project description:Bcl-2-accociated transcription factor 1(BCLAF1) has been shown to be involved in multiple biological processes. Transcript variants encoding different isoforms that are generated by alternative splicing have been found for this gene, but little is known about the mechanisms governing its splicing regulation and whether the misregulation is associated with cancer development. Mechanistic analysis revealed that splicing factor SRSF10 specifically interacts with exon5a and activates its inclusion, as RNAi-mediated knockdown of SRSF10 induced a dramatic skipping of exon5a. To define a comprehensive programm of alternative splicing that is regulated by SRSF10 in RKO cells, we used RNA-seq coupled with a bioinformatic analysis to identify the extensive splicing network regulated by SRSF10 in RKO cells.
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