SOX9 modulates cancer biomarker and cilia genes in pancreatic cancer
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA705089 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR13790200.fastq.gz | Fastqsanger.gz | |||
| SRR13790201.fastq.gz | Fastqsanger.gz | |||
| SRR13790202.fastq.gz | Fastqsanger.gz | |||
| SRR13790203.fastq.gz | Fastqsanger.gz | |||
| SRR13790204.fastq.gz | Fastqsanger.gz |
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Project description:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with high mortality. The cellular origins of PDAC are largely unknown, however, ductal cells, especially centroacinar cells (CACs), have several characteristics in common with PDAC, such as expression of SOX9 and components of the Notch-signaling pathway. Mutations in KRAS and alterations to Notch signaling are common in PDAC; and, both these pathways regulate the transcription factor SOX9. To identify genes regulated by SOX9, we performed siRNA knockdown of SOX9 followed by RNA-seq in PANC-1 cells, a human PDAC cell line. We report 93 differentially expressed (DE) genes, with convergence on alterations to Notch-signaling pathways and ciliogenesis. These results point to SOX9 and Notch activity being in a positive feedback loop; and, SOX9 regulating cilia production in PDAC. We additionally performed ChIP-seq in PANC-1 cells to identify direct targets of SOX9 binding and integrated these results with our DE gene list. Nine of the top ten downregulated genes have evidence of direct SOX9 binding at their promoter regions. One of these targets was the cancer stem cell marker EpCAM. Using whole-mount in situ hybridization to detect epcam transcript in zebrafish larvae, we demonstrated that epcam is a CAC marker and that Sox9 regulation of epcam expression is conserved in zebrafish. Additionally, we generated an epcam null mutant and observed pronounced defects in ciliogenesis during development. Our results provide a link between SOX9, EpCAM, and ciliary repression that can be exploited in improving our understanding of the cellular origins and mechanisms of PDAC.
2021-02-27 | GSE167590 | GEO
Project description:Pancreatic ductal adenocarcinoma (PDAC) is an aggressive form of cancer with high mortality. The cellular origins of PDAC are largely unknown; however, ductal cells, especially centroacinar cells (CACs), have several characteristics in common with PDAC, such as expression of SOX9 and components of the Notch-signaling pathway. Mutations in KRAS and alterations to Notch signaling are common in PDAC, and both these pathways regulate the transcription factor SOX9. To identify genes regulated by SOX9, we performed siRNA knockdown of SOX9 followed by RNA-seq in PANC-1s, a human PDAC cell line. We report 93 differentially expressed (DE) genes, with convergence on alterations to Notch-signaling pathways and ciliogenesis. These results point to SOX9 and Notch activity being in a positive feedback loop and SOX9 regulating cilia production in PDAC. We additionally performed ChIP-seq in PANC-1s to identify direct targets of SOX9 binding and integrated these results with our DE gene list. Nine of the top 10 downregulated genes have evidence of direct SOX9 binding at their promoter regions. One of these targets was the cancer stem cell marker EpCAM. Using whole-mount in situ hybridization to detect epcam transcript in zebrafish larvae, we demonstrated that epcam is a CAC marker and that Sox9 regulation of epcam expression is conserved in zebrafish. Additionally, we generated an epcam null mutant and observed pronounced defects in ciliogenesis during development. Our results provide a link between SOX9, EpCAM and ciliary repression that can be exploited in improving our understanding of the cellular origins and mechanisms of PDAC.
| S-EPMC8101357 | biostudies-literature
Project description:Understanding biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumors is essential, as tumor biomarkers, prognostic factors and therapeutics are all lacking. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (n = 22), malignant peripheral nerve sheath tumor (MPNST) cell lines (n = 13), benign neurofibromas (n = 26) and MPNST (n = 6). Dermal and plexiform neurofibromas were indistinguishable. A prominent theme in the analysis was aberrant differentiation. Neurofibromas repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes upregulated in the sarcomas were significantly enriched for genes activated in neural crest cells. We validated differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in neurofibroma and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumors - caused MPNST cell death. SOX9 is a biomarker of neurofibroma and MPNST, and possibly a therapeutic target in NF1. Keywords: tumor stage 86 microarrays, consisting of 77 samples and 9 batch reference samples: NHSC (10), dNFSC (11), pNFSC (11), MPNST cell lines (13), dNF (13), pNF (13), MPNST (6)
2009-07-15 | E-GEOD-14038 | biostudies-arrayexpress
Project description:Understanding biological pathways critical for common neurofibromatosis type 1 (NF1) peripheral nerve tumors is essential, as tumor biomarkers, prognostic factors and therapeutics are all lacking. We used gene expression profiling to define transcriptional changes between primary normal Schwann cells (n = 10), NF1-derived primary benign neurofibroma Schwann cells (n = 22), malignant peripheral nerve sheath tumor (MPNST) cell lines (n = 13), benign neurofibromas (n = 26) and MPNST (n = 6). Dermal and plexiform neurofibromas were indistinguishable. A prominent theme in the analysis was aberrant differentiation. Neurofibromas repressed gene programs normally active in Schwann cell precursors and immature Schwann cells. MPNST signatures strongly differed; genes upregulated in the sarcomas were significantly enriched for genes activated in neural crest cells. We validated differential expression of 82 genes including the neural crest transcription factor SOX9 and SOX9 predicted targets. SOX9 immunoreactivity was robust in neurofibroma and MPSNT tissue sections and targeting SOX9 - strongly expressed in NF1-related tumors - caused MPNST cell death. SOX9 is a biomarker of neurofibroma and MPNST, and possibly a therapeutic target in NF1. Keywords: tumor stage
2009-07-15 | GSE14038 | GEO
Project description:lung cancer biomarker Raw sequence reads
| PRJNA746114 | ENA
Project description:Background: Whereas cilia damage and reduced cilia beat frequency have been implicated as causative of reduced mucociliary clearance in smokers, theoretically mucociliary clearance could also be affected by cilia length. Based on models of mucociliary clearance predicting cilia length must exceed the 6 -7 μm airway surface fluid depth to generate force in the mucus layer, we hypothesized cilia height may be decreased in airway epithelium of normal smokers compared to nonsmokers. Methodology/Principal Findings: Cilia length in normal nonsmokers and smokers was evaluated in aldehyde-fixed, paraffin-embedded endobronchial biopsies, and air-dried and hydrated samples brushed from human airway epithelium via fiberoptic bronchoscopy. In 28 endobronchial biopsies, healthy smoker cilia length was reduced 15% compared to nonsmokers (p<0.05). In 47 air-dried samples of airway epithelial cells, smoker cilia length was reduced 13% compared to nonsmokers (p<0.0001). Analysis of the length of individual, detached cilia in 17 samples, smoker cilia length was reduced 9% compared to nonsmokers (p<0.05). Finally, in 16 fully hydrated, unfixed samples, smoker cilia length was reduced 7% compared to nonsmokers (p<0.05). Conclusions/significance: Models predict that a reduction in cilia length would reduce mucociliary clearance, suggesting that smoking-associated shorter airway epithelial cilia plays a significant role in the pathogenesis of smoking-induced lung disease.
2012-12-13 | E-GEOD-16696 | biostudies-arrayexpress
Project description:Aberrant expression of SOX9 in human colorectal cancer cells suggests its roles in the development of colorectal cancer. To gain insight into SOX9-mediated transcriptional regulation in colorectal cancer cells, we attempted to identify its physiological targets on a genome-scale using chromatin immunoprecipitation (ChIP) followed by sequencing (ChIP-seq) in HT-29, human colorectal cancer cells. SOX9 CHIP-seq was carried out using HT-29 cells.
2015-06-08 | E-GEOD-63629 | biostudies-arrayexpress
Project description:Heart valve formation initiates when endothelial cells of the heart transform into mesenchyme and populate the cardiac cushions. The transcription factor, SOX9, is highly expressed in the cardiac cushion mesenchyme, and is essential for heart valve development. Loss of Sox9 in mouse cardiac cushion mesenchyme alters cell proliferation, embryonic survival, and disrupts valve formation. Despite this important role, little is known regarding how SOX9 regulates heart valve formation or its transcriptional targets. Therefore, we mapped putative SOX9 binding sites by ChIP-Seq in embryonic day (E) 12.5 heart valves, a stage at which the valve mesenchyme is actively proliferating and initiating differentiation. Embryonic heart valves have been shown to express a high number of genes that are associated with chondrogenesis, including several extracellular matrix proteins and transcription factors that regulate chondrogenesis. Consequently, we compared regions of putative SOX9 DNA-binding between E12.5 heart valves and E12.5 limb buds. We identified context-dependent and contextâindependent SOX9 interacting regions throughout the genome. Analysis of context-independent SOX9 binding suggests an extensive role for SOX9 across tissues in regulating proliferation-associated genes including key components of the AP-1 complex. Integrative analysis of tissue-specific SOX9 interacting regions and gene expression profiles on Sox9-deficient heart valves demonstrated that SOX9 controls the expression of several transcription factors with previously identified roles in heart valve development, including Twist1, Sox4, Mecom/Evi1 and Pitx2. Together, our data identifies SOX9 coordinated transcriptional hierarchies that control cell proliferation and differentiation during valve formation. Examination of SOX9 binding sites in E12.5 atrioventricular canal (AVC) and E12.5 embryonic limb and mRNA expression profiling in E12.5 WT and Sox9 mutant AVCs, in duplicate.
2015-11-05 | E-GEOD-73225 | biostudies-arrayexpress
Project description:Epigenetic dysregulation is a universal feature of cancer that results in altered patterns of gene expression that drive malignancy. Brain tumors exhibit subtype-specific epigenetic alterations, however the molecular mechanisms responsible for these diverse epigenetic states remain unclear. Here we show that the developmental transcription factor Sox9 differentially regulates epigenomic states in high-grade glioma (HGG) and ependymoma (EPN). These contrasting roles for Sox9 correspond with protein interactions with histone deacetylating complexes in HGG, and association with the Rela oncofusion in EPN. Together, our studies demonstrate how epigenomic states are differentially regulated in distinct subtypes of brain tumors, while revealing divergent roles for Sox9 in HGG and EPN tumorigenesis.
2022-07-13 | PXD033863 | Pride
Project description:SOX9 is critical for prostate development and is implicated in prostate cancer, we used transcriptome profiling in combination with SOX9 ChIP-seq to identify genes and pathways it regulates in normal or neoplastic epithelium. We used microarrays to detail the global programme of gene expression in TMPRSS2/ERG fusion positive prostate cancer cell line with high basal expression of SOX9 by comparing the expression changes between SOX9 knockdown versus control.
2016-12-28 | GSE76441 | GEO