Fascin actin-bundling protein 1 regulates non-small cell lung cancer progression by influencing transcription and splicing of tumorigenesis-related genes [IRIP-seq]
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ABSTRACT:
PROVIDER: PRJNA983357 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR24911862_1.fastq.gz | Fastqsanger.gz | |||
| SRR24911862_2.fastq.gz | Fastqsanger.gz | |||
| SRR24911863_1.fastq.gz | Fastqsanger.gz | |||
| SRR24911863_2.fastq.gz | Fastqsanger.gz | |||
| SRR24911864_1.fastq.gz | Fastqsanger.gz |
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Project description:Fascin actin-bundling protein 1 regulates non-small cell lung cancer progression by influencing transcription and splicing of tumorigenesis-related genes
| PRJNA983342 | ENA
Project description:Fascin actin-bundling protein 1 regulates non-small cell lung cancer progression by influencing transcription and splicing of tumorigenesis-related genes [RNA-seq]
| PRJNA983358 | ENA
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:Fascin-1 mediated actin-bundling activity is central to the generation of plasma membrane protrusions required for cell migration. Dysregulation of cellular protrusions is observed in metastatic cancers, where they are required for increased invasiveness, and this is often correlated with overexpression of Fascin-1. Therefore, there is interest in generating therapeutic Fascin-1 inhibitors. We present the identification of Nb 3E11, a nanobody inhibitor of Fascin-1 actin-bundling activity, filopodia formation and cell migration. The crystal structure of the Fascin-1/Nb 3E11 complex reveals the structural mechanism of inhibition. Nb 3E11 occludes an actin-binding site on the third -trefoil domain of Fascin-1 that is currently untargeted by chemical inhibitors and induces a conformational change in the adjacent domains to stabilise Fascin-1 in an inhibitory state similar to that adopted in the presence of small molecule inhibitors. Nb 3E11 can be utilised as a tool inhibitor molecule to aid in the development of Fascin-1 targeted therapeutics.
2024-03-25 | PXD038713 | Pride
Project description:Colorectal cancer (CRC) is a highly malignant tumor associated with a poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR expresses at a higher level in CRC than normal tissue and LYAR expression is closely associated with distant CRC metastasis. LYAR significantly promotes the migration and invasion of CRC cells in vitro, and reduction of LYAR expression in CRC cells inhibites xenograft tumor metastasis in vivo. Microarray analysis of LYAR knockdown (KD) cells combined with ChIP assay, gene reporter assay and rescue experiment indicate that FSCN1 (fascin actin-bundling protein 1, Fascin-1) serves as a new and key regulator of the LYAR-promoted migration and invasion of CRC cells. In addition, knockdown of FSCN1 significantly inhibites subcutaneous tumorigenesis of CRC cells. Moreover, we found that FSCN1 affects some key enzymes in lipid fatty acid metabolism such as FASN and SCD. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by up-regulating FSCN1 expression and further promoting fatty acid synthesis in CRC.
2021-07-26 | GSE180805 | GEO
Project description:Cell-cell fusion is a frequent and essential event during development, and its dysregulation causes diseases ranging from infertility to muscle weakness. Fusing cells repeatedly need to remodel their plasma membrane by orchestrated formation and disassembly of cortical actin filaments, but how the dynamic reorganization of the actin cytoskeleton control is still poorly understood. Here, we identified a ubiquitin- dependent toggle switch that establishes reversible actin bundling during mammalian cell fusion. We found that EPS8-IRSp53 complexes stabilize cortical actin bundles at sites of cell contact, which in part pushes cells towards each other. Conversely, EPS8 monoubiquitylation by CUL3KCTD10 displaces EPS8-IRSp53 from membranes and counteracts actin bundling, a dual activity that allows apposed cells to progress with fusion. We conclude that cytoskeletal rearrangements during development are precisely controlled by ubiquitylation, raising the possibility to modulate the efficiency of cell-cell fusion for therapeutic benefit.
2020-12-22 | GSE161681 | GEO
Project description:The actin-bundling protein fascin (FSCN1) is overexpressed in aggressive adrenocortical carcinoma (ACC) and represents a reliable prognostic indicator. We investigated the effects of FSCN1 inactivation by CRISPR/Cas9 in ACC H295R cells on global gene expression profiles in those cells. We performed gene expression profiling analysis using data obtained from RNA-seq of 2 different H295R control clones and 2 different FSCN1 KO clones (2 biological replicates for each clone).
2022-10-25 | GSE216008 | GEO
Project description:Project 1: The deregulation of the actin cytoskeleton has been extensively studied in metastatic dissemination. However, the post-dissemination role of the actin cytoskeleton dysregulation is poorly understood. Here we report that fascin, an actin-bundling protein, promotes lung cancer metastatic colonization by augmenting metabolic stress resistance and mitochondrial OXPHOS. Fascin is directly recruited to mitochondria under metabolic stress to stabilize mitochondrial actin filaments (mtF-actin). Using unbiased metabolomics and proteomics approaches, we discovered that fascin-mediated mtF-actin remodeling promotes mitochondrial OXPHOS by increasing the biogenesis of respiratory Complex I. Mechanistically, fascin and mtF-actin controls the homeostasis of mtDNA to promote mitochondrial OXPHOS. The disruption of mtFactin abrogates fascin-mediated lung cancer metastasis. Conversely, restoration of mitochondrial respiration using yeast NDI1 in fascin depleted cancer cells is able to rescue lung metastasis. Our findings indicate that the dysregulated actin cytoskeleton in metastatic lung cancer could be targeted to rewire mitochondrial metabolism and to prevent metastatic recurrence. Project 2: There is a pool of mitochondrial dNTP in the cell maintained by the mitochondrial deoxynucleoside salvage pathway and dedicated for the mtDNA homeostasis in slow-cycling and post-mitotic cells. The role of the mitochondrial deoxynucleoside salvage pathway in tumor initiation and progression is poorly understood. Here, we investigated the role of the mitochondrial deoxyguanosine kinase (DGUOK), a rate-limiting enzyme in the mitochondrial deoxynucleoside salvage pathway, in the self-renewal of lung adenocarcinoma cancer stem-like cells (CSC). Our data support that DGUOK overexpression strongly correlates with cancer progression and patient survival. The depletion of DGUOK robustly inhibited lung adenocarcinoma tumor growth, metastasis and CSC self-renewal. Mechanistically, DGUOK is required for the biogenesis of respiratory Complex I and mitochondrial OXPHOS, which in turn regulates CSC self-renewal through AMPK-YAP1 signaling. The restoration of mitochondrial OXPHOS in DGUOK depleted lung cancer cells using NDI1, a single subunit yeast NADH : ubiquinone oxidoreductase, was able to rescue AMPK-YAP1 signaling and CSC stemness. Genetic targeting of DGUOK using doxycycline-inducible CRISPR/Cas9 was able to markedly induce tumor regression. Our findings reveal a novel role for mitochondrial dNTP metabolism in lung cancer tumor growth and progression, and implicate that the mitochondrial deoxynucleotide salvage pathway could be potentially targeted to prevent CSC-mediated therapy resistance and metastatic recurrence.
2019-09-12 | PXD014753 | Pride
Project description:Colorectal cancer (CRC) is a highly malignant tumor associated with poor prognosis, yet the molecular mechanisms are not fully understood. In this study, we showed that LYAR, a nucleolar protein, expresses at a higher level in CRC than adjacent normal tissue and LYAR expression is closely associated with distant CRC metastasis. LYAR not only significantly promotes the migration and invasion of CRC cells in vitro, also the knockdown (KD) of LYAR in CRC cells inhibits xenograft tumor metastasis in vivo. Microarray analysis of LYAR KD cells combined with ChIP assay, gene reporter assay and rescue experiment indicate that FSCN1 (encoding fascin actin-bundling protein 1, Fascin-1) serves as a new key regulator of the LYAR-promoted migration and invasion of CRC cells. Knockdown of FSCN1 significantly inhibits subcutaneous tumorigenesis of CRC cells, and leads to the down-regulation of FASN and SCD, genes encoding key enzymes in fatty acid synthesis. In summary, this study reveals a novel mechanism by which LYAR promotes tumor cell migration and invasion by up-regulating FSCN1 expression and affecting fatty acid metabolism in CRC.
2021-07-17 | GSE180263 | GEO