CRKL regulates alternative splicing of genes that function in tumorigenesis and cancer progression
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ABSTRACT:
PROVIDER: PRJNA495833 | ENA |
REPOSITORIES: ENA
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Project description:CRKL adaptor protein was demonstrated to have important effects in various types of human cancer and contributes to malignant cell growth and chemoresistance as an overexpressed oncoprotein in cervical carcinoma. But the special molecular mechanisms of CRKL in cervical cancer remain unknown. Here we reported that CRKL regulates genes in cervical cancer related pathways via targeting alternative splicing. We analyzed the expression level of CRKL in 300 cervical cancer tissue samples available in TCGA database, showing a significant increase expression in Stage I cancer samples. From these tumor samples, we selected 40 cancer samples with 20 showing high CRKL expression and 20 showing low, which were analyzed for the potential impact of CRKL on alternative splicing regulation of cancer transcriptome. We further explored the potential function of CRKL in promoting cell proliferation and regulating alternative splicing in HeLa cells using shRNA to knock-down CRKL expression. More importantly, we showed that 34 (94%) of CRKL-regulated alternative splicing events detected in HeLa cells could be validated by qPCR approach and more than a half of these validated events detected in HeLa cells were also correlated with the CRKL expression level in cervical cancers. These results together support a conclusion that CRKL adaptor protein extensively regulates alternative splicing of many genes which are important in tumorigenesis and cancer progression, which expands the functional importance of signaling adaptors in coordinating the dynamic activation of signaling pathways with cellular responses at the alternative splicing level.
2019-06-10 | GSE120631 | GEO
Project description:Splicing factor SRSF1 promotes breast cancer progression via regulating alternative splicing
| PRJNA684349 | ENA
Project description:The metabolic conversion of oxidative phosphorylation to glycolysis provides tumor cells with energy and biosynthetic substrates, thereby promoting tumorigenesis and malignant progression. However, the mechanisms controlling the tumor metabolic switch is still not entirely clear. Here we demonstrate that SAM68 (gene name: KHDRBS1) as a splicing regulatory factor is frequently overexpressed in Lung adenocarcinoma (LUAD) and negatively correlated with the prognosis of LUAD patients. we find SAM68 promotes LUAD cells tumorigenesis and metastasis both in vitro and in vivo by regulating cancer metabolic switch. SAM68 drives cancer metabolism by mediating alternative splicing of Pyruvate kinase (PKM) pre-mRNAs, finally promoting the formation of PKM2. Mechanically, Sam68 interacted with the splicing repressor hnRNP A1, and depletion of hnRNP A1 or mutations that impair this interaction attenuated the PKM splicing regulation. Together, our work demonstrates key roles of SAM68 in the cancer metabolic conversion by regulating alternative splicing and SAM68 may be a promising therapeutic target for treating LUAD.This project looks into how SAM68 levels affect cancer cell phenotype in vitro
2020-11-04 | GSE149120 | GEO
Project description:DIS3-like 3'-5' exoribonuclease 2 (DIS3L2) degrades aberrant RNAs, however, its function in tumorigenesis remains largely unexplored.hnRNP U regulates the alternative splicing of pre-mRNA, and our results also showed that RNA promoted the interaction between DIS3L2 and hnRNP U, suggesting that DIS3L2 may be involved in splicing regulation. Thus, we next performed RNA-Seq to investigate whether DIS3L2 regulated pre-mRNA alternative splicing in cancer cells.
2020-01-01 | GSE133759 | GEO
Project description:We analyzed a role of Brd2 protein in transcription and alternative splicing. 289 genes change alternative splicing after Brd2 knockdown and 1459 genes alter gene expression compared to cells treated with negative control siRNA. 6 samples (3 independent samples of cells treated with Brd2 siRNA, 3 samples of cells treated with negative control siRNA)
2013-12-03 | E-GEOD-39937 | biostudies-arrayexpress
Project description:Drak2 Regulates RNA Alternative Splicing by Suppressing SRPK1-SRSF6 Signaling Pathway
2021-09-17 | PXD028609 | iProX
Project description:This SuperSeries is composed of the following subset Series: GSE30995: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [RNA-Seq] GSE31006: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [ChIP-Seq] GSE31007: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [protein binding microarray] GSE31948: An Alternative Splicing Switch Regulates Embryonic Stem Cell Pluripotency and Reprogramming [AS microarray] Refer to individual Series
2011-09-14 | E-GEOD-30992 | biostudies-arrayexpress
Project description:Although Sm-like proteins (LSMs) form the core of U6 RNPs and function in pre-mRNA splicing, little is known regarding their regulatory role in selection of splice sites, alternative splicing (AS) and splicing efficiency in eukaryotes. The Arabidopsis SAD1 locus encodes the LSM5 protein and was defined in a genetic screen for components that regulate the expression of stress-responsive gene. To further investigate regulatory role of the protein SAD1 in pre-mRNA splicing, we performed RNA sequencing (RNA-seq) to examine the changes of the global alternative splicing (AS) among the wildtype Arabidopsis plant (C24), the mutant plant (sad1) and the sad1-overexpressed plant (SAD1-OE). Our work not only provided novel insights into the regulatory role of SAD1 or LSM proteins in splicing, but also provided new cues to improving splicing efficiency and optimizing biological functions and screening the stress-resistant plant.
2013-11-01 | E-MTAB-4336 | biostudies-arrayexpress
Project description:We analyzed a role of Brd2 protein in transcription and alternative splicing. 289 genes change alternative splicing after Brd2 knockdown and 1459 genes alter gene expression compared to cells treated with negative control siRNA.
2013-12-03 | GSE39937 | GEO
Project description:Neuronal alternative splicing is a key gene regulatory mechanism in brain. Yet the spliceosome machinery is insufficient to fully specify splicing complexity. In considering the role of the epigenome in activity-dependent alternative splicing, we and others find the histone modification, H3K36me3, to be a putative splicing regulator. In the current study, we found that mouse cocaine self-administration caused widespread differential alternative splicing, concomitant with enrichment of H3K36me3 at differentially spliced junctions. Importantly, only targeted epigenetic editing can distinguish between a direct role of H3K36me3 in splicing and an indirect role via regulation of splice factor expression elsewhere on the genome. We targeted Srsf11, which was both alternatively spliced and H3K36me3 enriched in brain following cocaine self-administration. Results: Epigenetic editing of H3K36me3 at Srsf11 was sufficient to drive its alternative splicing and enhanced cocaine self-administration, establishing the direct causal relevance of H3K36me3 to alternative splicing of Srsf11 and to reward behavior.
2021-07-31 | GSE180988 | GEO