Filamin B extensively regulates the transcription and alternative splicing and is associated with apoptosis in HeLa cells
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ABSTRACT:
PROVIDER: PRJNA556368 | ENA |
REPOSITORIES: ENA
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Project description:Post-transcriptional mechanisms is an important means for the body to fight against cancer, and it may also be hijacked by tumor cells to help them adapt to local microenvironment. Filamin B (FLNB), an actin-binding protein and providing crucial scaffolds for cell motility and signaling, was also identified as one of RNA binding proteins (RBPs). Recent works showed that FLNB might play important role not only in skeletal development but also in the regulation of tumorigenesis. However, the effects of dysregulated expression of FLNB at a molecular level are unclear. In this study, we used RNA-seq to analyze the global transcriptional level changes and alternative splicing between the knocked-down FLNB and the control in Hela cells. Reduced levels of FLNB led to a significant decrease in cell apoptosis, compared with control cells. FLNB knockdown extensively regulated the expression of genes in cell apoptosis, tumorigenesis, metastases, transmembrane transport, cartilage and nerve development. Moreover, FLNB regulated alternative splicing of a large number of genes enriched in cell death and apoptotic process. Meanwhile, some genes and alternative splicing related to skeletal development were enriched and regulated by FLNB. Quantitative RT-PCR confirmed the FLNB-regulated transcription and alternative splicing. This study provides the first transcriptome-wide analysis of FLNB. Our findings indicated that FLNB may play an important regulatory role in cancer cell apoptosis via the regulation of alternative splicing and potentially transcription, which greatly expands the current understanding of the mechanisms of FLNB mediated gene regulation.
2020-05-19 | GSE134769 | GEO
Project description:RNA binding proteins (RBPs) are key players of genome regulation. Here we report the transcriptome study of HnRNP D-Like protein, which belongs to the hnRNP family. We used RNA-seq to analyze the global transcript level and alternative splicing on hnRNPDL shRNA-treated cells and control. Sh-hnRNPDL extensively increased in the expression of genes involved in female pregnancy, cell apoptosis, cell proliferation and cell migration. HnRNPDL regulated alternative splicing of hundreds of genes enriched in transcription regulation and signalling pathways including NOD-like receptor signaling, Notch signaling, and TNF signaling. This study provides the first transcriptome-wide analysis of hnRNPDL regulation of gene expression, which adds to the understanding of critical hnRNPDL functions.
2020-12-22 | GSE108728 | GEO
Project description:hnRNPDL extensively regulates transcription and alternative splicing
| PRJNA428381 | ENA
Project description:Cytokeratin 18(CK18), one of the major components of intermediate filaments (IF) in simple-type epithelial cells, has been used as the biomarker of several cancers. CK18 has been also reported to be dysregulated in cervical cancers, however, the precise molecular pathways regulated by CK18 remained elusive. In this study, CK18 was knockdown in Hela cells and which led to a significantly decrease of cell apoptosis compared with control cells. The global transcript profile and alternative splicing of CK18 knockdown cells and control were analyzed. A total of 593 differentially expressed genes were identified, and these genes were mainly involved in synaptic transmission, immune response, innate immune response, signal transduction pathways. Strikingly, hundreds of genes were regulated by CK18, which mainly enriched in immune and apoptosis related pathways. In conclusion, our study indicates that CK18 plays important regulatory role in cervical cancers in transcriptional level as well as alternative splicing regulation.
2019-06-16 | GSE119255 | GEO
Project description:RNA binding proteins have important functions in tumorigenesis; therefore, their regulatory mechanisms should be further explored. The present study aimed to determine the regulatory roles of RNA binding motif protein 6 (RBM6) in transcription and alternative splicing in Hela cells. RBM6 expression levels and its effect on the prognosis of different tumors in The Cancer Genome Atlas database were analyzed using TIMER2.0. Short hairpin RNA was used to ablate RBM6 expression in HeLa cells. Differentially expressed genes and alternative splicing events in Hela cells were assessed using RNA sequencing and quantitative real-time reverse transcription polymerase chain reaction. RBM6 was identified as a prognostic marker for bladder urothelial carcinoma, kidney renal clear cell carcinoma, mesothelioma, and pancreatic adenocarcinoma. Knockdown of RBM6 promoted cell proliferation. In Hela cells, RMB6 regulated the expression and alternative splicing of many genes involved in tumorigenesis_x001E_related pathways, including ‘apoptotic process’, ‘mitotic cell cycle’, and ‘RNA splicing’. RBM6-regulated alternatively spliced genes (DIABLO (Diablo IAP-binding mitochondrial protein), PAK4 (P21 (RAC1) activated kinase 4) and ERCC2 (ERCC excision repair 2, TFIIH core complex helicase subunit)) were subjected to quantitative real-time reverse transcription polymerase chain reaction validation, which demonstrated the same expression trends as the RNA sequencing results. Our findings showed that RBM6 affects tumorigenesis and cancer progression by disrupting alternative splicing in HeLa cells.
2023-10-17 | GSE196600 | GEO
Project description:Objective: In our study, we aimed to explore the molecular mechanism of RPL8 in tumors by analyzing over-expression of RPL8 in HeLa cells. Method: Two experimental groups and control groups were setup. The experimental groups adopted Hela cells transfected by RPL8 plasmid , and the control group used the Hela cells transfected by blank plasmid. The total mRNA of the cells were extracted after transfection for 48 hours and the expression level of mRNA was detected by using high-throughput sequencing technology. Then R Bioconductor software package edgeR was used to screen differentially expressed genes and TopHat2 was used to analyze the splice site of each sample. Finally, GO and KEGG analysis of differentially expressed genes and differential alternative splicing events were performed, and the top ten functional pathways were selected for display. Results: Overexpression of RPL8 produced a large number of differentially expressed genes and differential alternative splicing. Many of these differentially expressed genes and differential alternative splicing genes were enriched in tumor-related pathways, including inflammation, positive regulation of cell proliferation , Angiogenesis, etc. In addition, many of these differentially expressed genes have been shown to be closely related to the occurrence and development of tumors. Conclusion: RPL8 can widely regulate the expression and alternative splicing of tumor-related genes.
2024-01-03 | GSE161696 | GEO
Project description: Not available
| S-EPMC7108129 | biostudies-literature
Project description:Alternative splicing profiling of apopotosis related genes in human HeLa cells (cervical cancer cell line) transfected with a plasmid expressing shRNAs targetting p68 helicase (DDX5, DEAD (Asp-Glu-Ala-Asp) box polypeptide 5) cloned into the pSuper expression vector compared to empty vector. Keywords: treated vs. untreated comparison; alternative splicing
2011-01-21 | GSE20010 | GEO
Project description:We report a comprehensive analysis of alterations in gene expression and alternative splicing upon RBM39 depletion and rescue in HeLa cells.
2023-06-19 | GSE202134 | GEO
Project description:RNA-binding proteins (RBPs) have important roles in orchestrating posttranscriptional regulation and modulating many tumorigenesis events. SERBP1 has been recognized as an important regulator in multiple cancers, while it remains unclear whether SERBP1-regulated gene expression at the transcriptome-wide level is significantly correlated with tumorigenesis.We overexpressed SERBP1 in HeLa cells and explored whether SERBP1 overexpression (SERBP1-OE) affects the proliferation and apoptosis of HeLa cells. We analyzed the transcriptome-wide gene expression changes and alternative splicing changes mediated by SERBP1-OE using transcriptome sequencing method (RNA-seq). RT-qPCR was conducted to assay SERBP1-regulated alternative splicing.SERBP1-OE induced the apoptosis of HeLa cells. The downregulated genes were strongly enriched in the cell proliferation and apoptosis pathways according to the GO analysis, including FOS, FOSB, PAK6 and RAB26. The genes undergoing at least one SERBP1-regulated alternative splicing event were enriched in transcriptional regulation, suggesting a mechanism of the regulation of gene expression, and in pyruvate and fatty acid metabolic processes critical for tumorigenesis events. The SERBP1-regulated alternative splicing of ME3, LPIN3, CROT，PDP1, SLC27A1 and ALKBH7 was validated by RT-qPCR analysis.We for the first time demonstrated the cellular function and molecular targets of SERBP1 in HeLa cells at transcriptional and post-transcriptional levels. The SERBP1-regulated gene expression and alternative splicing networks revealed by this study provide important information for exploring the functional roles and regulatory mechanisms of SERBP1 in cancer development and progression.
2022-09-02 | GSE192950 | GEO