Regulation of alternative splicing induced by paclitaxel in human non-small cell lung cancer
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE107676 | GEO | 2018/06/20
REPOSITORIES: GEO
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Project description:Regulation of alternative splicing induced by paclitaxel in human non-small cell lung cancer
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Project description:CELF6 (CUGBP Elav-Like Family Member 6), a typical RNA binding protein, can regulate alternative splicing of pre-mRNAs, and may also participate in mRNA editing and translation. As a tumor suppressor, CELF6 is abnormally low expressed in colon cancer, breast cancer and other tumors, and is closely related to proliferation, invasion, and migration. Recent studies have shown that CELF6 has abnormally low expression in lung cancer tissues, and is increased after ultra-hypoxia treatment in A549 cells, however, the functions and molecular mechanisms of CELF6 in lung cancer are still unclear. We overexpressed CELF6 in human non-small cell lung cancer cells (A549), and set up a control; after collecting cells, we used RNA sequencing to screen for genes with significant differential expression (DEGs) after CELF6 overexpression, and significantly alternative splicing events (ASEs). CELF6 overexpression widely regulates the expression of related genes in immune response，Inflammation response, Innate immune response，TNF signaling pathway, cell adhesion molecules (CAMs) and so on. We found that CELF6 can inhibit the expression many immune-related genes, such as TNFSF10、CCL5、JUNB、BIRC3、MLKL、PIK3R2、CCL20、STAT1、MYD88 and CFS1，which mainly function in promoting tumorigenesis in lung cancer. These DEGs were validated by reverse transcriptase quantitative polymerase chain reaction (RT-PCR). In addition, CELF6 regulates the alternative splicing of a large number of genes which were enriched in p53 signaling pathway and apoptosis，such as TP53 and CD44. This study is the first to analyze the transcriptome analysis of differential gene expression and alternative splicing of CELF6 overexpression. which will provide a new idea for the gene regulation mechanism mediated by CELF6 in the production and development of NSCLC.
2022-07-11 | GSE185865 | GEO
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
Project description:Background. High mortality rates are prevalent among patients with non-small cell lung cancer (NSCLC), and effective therapeutic targets are key prognostic factors. Fascin actin-bundling protein 1 (FSCN1) promotes NSCLC; however, its role as an RNA-binding protein in NSCLC remains unexplored. Therefore, we aimed to explore FSCN1 expression and function in A549 cells. Method. We screened for alternative-splicing events and differentially expressed genes (DEGs) after FSCN1 silence via RNA-sequencing (RNA-seq). FSCN1 immunoprecipitation followed by RNA-seq were used to identify target genes whose mRNA expression and pre-mRNA alternative-splicing levels might be influenced by FSCN1. Results. Silencing FSCN1 in A549 cells affected malignant phenotypes; it inhibited proliferation, migration, and invasion, and promoted apoptosis. RNA-seq analysis revealed 2851 DEGs and 3057 alternatively spliced genes. Gene ontology-based functional enrichment analysis showed that downregulated DEGs and alternatively splicing genes were enriched for the cell-cycle. FSCN1 promoted the alternative splicing of cell-cycle-related mRNAs involved in tumorigenesis (i.e., BCCIP, DLGAP5, PRC1, RECQL5, WTAP, and SGO1). Combined analysis of FSCN1 RNA-binding targets and RNA-seq data suggested that FSCN1 might affect ACTG1, KRT7, and PDE3A expression by affecting the pre-mRNA alternative-splicing levels of NME4, NCOR2, and EEF1D FSCN1 to long non-coding RNA transcripts (RNASNHG20, NEAT1, NSD2, and FTH1), which were highly abundant. Overall, extensive transcriptome analysis of gene alternative splicing and expression levels was performed in cells transfected with FSCN1 short-interfering RNA. Our data provide global insights into the regulatory mechanisms mediated by FSCN1 and its target genes in lung cancer.
2023-07-01 | GSE234859 | GEO
Project description:Background. High mortality rates are prevalent among patients with non-small cell lung cancer (NSCLC), and effective therapeutic targets are key prognostic factors. Fascin actin-bundling protein 1 (FSCN1) promotes NSCLC; however, its role as an RNA-binding protein in NSCLC remains unexplored. Therefore, we aimed to explore FSCN1 expression and function in A549 cells. Method. We screened for alternative-splicing events and differentially expressed genes (DEGs) after FSCN1 silence via RNA-sequencing (RNA-seq). FSCN1 immunoprecipitation followed by RNA-seq were used to identify target genes whose mRNA expression and pre-mRNA alternative-splicing levels might be influenced by FSCN1. Results. Silencing FSCN1 in A549 cells affected malignant phenotypes; it inhibited proliferation, migration, and invasion, and promoted apoptosis. RNA-seq analysis revealed 2851 DEGs and 3057 alternatively spliced genes. Gene ontology-based functional enrichment analysis showed that downregulated DEGs and alternatively splicing genes were enriched for the cell-cycle. FSCN1 promoted the alternative splicing of cell-cycle-related mRNAs involved in tumorigenesis (i.e., BCCIP, DLGAP5, PRC1, RECQL5, WTAP, and SGO1). Combined analysis of FSCN1 RNA-binding targets and RNA-seq data suggested that FSCN1 might affect ACTG1, KRT7, and PDE3A expression by affecting the pre-mRNA alternative-splicing levels of NME4, NCOR2, and EEF1D FSCN1 to long non-coding RNA transcripts (RNASNHG20, NEAT1, NSD2, and FTH1), which were highly abundant. Overall, extensive transcriptome analysis of gene alternative splicing and expression levels was performed in cells transfected with FSCN1 short-interfering RNA. Our data provide global insights into the regulatory mechanisms mediated by FSCN1 and its target genes in lung cancer.
2023-07-01 | GSE234858 | GEO
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
Project description:This SuperSeries is composed of the following subset Series: GSE23513: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB (HJAY) GSE23514: Position-dependent alternative splicing activity revealed by global profiling of alternative splicing events regulated by PTB (Exon array) Refer to individual Series
2010-09-01 | E-GEOD-23522 | biostudies-arrayexpress
Project description:Alternative polyadenylation has been implicated as an important regulator of gene expression. In some cases, alternative polyadenylation is known to couple with alternative splicing to influence last intron removal. However, it is unknown whether alternative polyadenylation events influence alternative splicing decisions at upstream exons. Knockdown of the polyadenylation factors CFIm25 or CstF64 was used as an approach in identifying alternative polyadenylation and alternative splicing events on a genome-wide scale. Although hundreds of alternative splicing events were found to be differentially spliced in the knockdown of CstF64, genes associated with alternative polyadenylation did not exhibit an increased incidence of alternative splicing. These results demonstrate that the coupling between alternative polyadenylation and alternative splicing is usually limited to defining the last exon. The striking influence of CstF64 knockdown on alternative splicing can be explained through its effects on UTR selection of known splicing regulators such as hnRNP A2/B1, thereby indirectly influencing splice site selection. We conclude that changes in the expression of the polyadenylation factor CstF64 influences alternative splicing through indirect effects. HeLa cell line was stably transfected with shRNA plasmids targeting CstF64. Total RNA was isolated from CstF64 KD cells and wild-type control cells using Trizol according to manufacturerâs protocols. Samples were deep sequenced in duplicate using the Illumina GAIIx system.
2016-03-14 | E-GEOD-79157 | biostudies-arrayexpress
Project description:Alternative splicing (AS) is particularly relevant to cancer progression and apoptosis. Although previous studies have shown that the apurinic-apyrimidinic endonuclease-1 (APEX1) is involved in tumor progression, it is unclear whether APEX1 can regulate AS on cell proliferation and apoptosis of Non-small-cell lung cancer (NSCLC). We performed a comprehensive analysis of the APEX1 expression in 517 lung NSCLC samples from the TCGA (Cancer Genome Atlas) database, and selected two sets of cancer samples with differentially expression APEX1 to analyze potential APEX1-regulated alternative splicing events (ASEs). Functional analysis of the APEX1 in A549 cells were performed in vitro. The APEX1 was overexpression in A549 cell by gene transfection. We identified AS targets regulated by APEX1, analyzed the GO biological process and KEGG functional pathways, and validated APEX1-regulated ASEs detected by RNA-seq and RT-PCR in A549 cells, then in clinical NSCLC samples these results were verified. The expression of the APEX1 was up-regulated in NSCLC samples, and overexpression of the APEX1 resulted in cell proliferation reduction and apoptosis induction. AS of many genes regulated by the APEX1 were enrich in cancer-related functional pathways. Results from A549 cell model and clinical samples showed that the MAPK signaling pathway, the Wnt signaling pathway were shared among the top ten enriched GO processes and KEGG functional pathways. According to our research, the validated AS events regulated by APEX1 mostly located in genes encoding transcription regulation factor in various signaling pathways, including the AXIN1 (axis inhibition protein 1), GCNT2 (N-acetyl glucosaminyl transferase 2), SMAD3 (SMAD Family Member 3), CTBP2 (C-Terminal Binding Protein 2). In this study, we successfully applied RNA-seq technology to demonstrate APEX1 regulation of AS. Our results underline that APEX1 was efficiently up-regulated in NSCLC samples, while overexpression of the APEX1 in A549 cells resulted in proliferation reduction and apoptosis induction. We confirm that the APEX1 regulates the AS of many genes which involved in cancer proliferation and apoptosis functional pathways, such as the MAPK signaling pathway and the Wnt signaling pathway, leading to mediate lung cancer progression. We found that high expression of the APEX1 in NSCLC is an independent prognostic factor related to tumor progression. Therefore, the APEX1 can serve as a molecular marker or therapeutic target for NSCLC treatment.
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Project description:We analyzed alternative splicing with Shh medulloblastoma. This dataset contains bam files of whole genome sequencing from 4 cases. Genomic DNA was isolated from both tumor and matched control specimens. We performed whole genome sequence on Illumina Hiseq.
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