Expression data in the human pancreatic cancer cell line RWP-1 subjected to SOX9 silencing
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE193406 | GEO | 2022/01/11
REPOSITORIES: GEO
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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.
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Project description:Expression data in the human pancreatic cancer cell line RWP-1 subjected to SOX9 silencing
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Project description:Our lab identified Sox9 as a specific marker and maintenance factor of mouse pancreatic progenitors (Seymour et al., PNAS, 2007). Here was wanted to identify direct targets of Sox9 in pancreatic progenitors. However, due to the limited number of pancreatic progenitors in the developing mouse, we used in vitro derived pancreatic progenitors to determine direct targets of Sox9. We performed ChIP-seq analysis for Sox9 and determined its direct targets in the human genome. Using pancreatic progenitors that were derived from human embryonic stem cells, we were able to successfully find targets that were pancreas specific as well as those targets that are important in other endodermal lineages.
2015-08-07 | GSE61947 | GEO
Project description:Sox9/Pdx1 co-regulated target genes were identified by comparing gene expression in Sox9/Pdx1-double heterozygates versus Sox9- or Pdx1- heterozygates pancreata using microarray analysis. Pdx1LacZko (herein designated Pdx1-/+) (Offield et al. 1996) and one Sox9 allele was conditionally deleted in the developing pancreas via recombination of a Sox9-flox allele (Kist et al., 2002) using the Foxa3-Cre transgene (Lee et al., 2005). Total RNA was isolated and pooled from dorsal pancreatic epithelia of e12.5 Sox9fl/+; Foxa3-Cre (Sox9 het), Pdx1-/+ (Pdx1 het) versus Sox9fl/+; Foxa3-Cre; Pdx1-/+ (Sox9/Pdx1 double hets) littermates for three biological replicates
2015-08-07 | E-GEOD-62023 | biostudies-arrayexpress
Project description:Sox9 target genes were identified by comparing gene expression in Sox9-ablated versus wild-type pancreata using microarray analysis. Sox9 was conditionally ablated in the developing pancreas via recombination of a Sox9-flox allele (Kist et al., 2002) using the Pdx1-Cre transgene (Gu et al., 2002). Total RNA was isolated and pooled from dorsal pancreatic epithelia of e12.5 Sox9fl/fl; Pdx1-Cre (mutant) versus Sox9fl/fl (wild-type) littermates for three biological replicates.
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Project description:Sorafenib is a multi-kinase blocker and one of the few suggested drug treatments for aggressive hepatocellular carcinoma (HCC) patients. However, drug resistance to sorafenib may often occur over time and cause further tumor aggression. Recently, cancer stem cells were found in HCC and were speculated to be involved in tumor progression. SOX9 is highly expressed in HCC cancer stem cells and promotes cell proliferation and self-renewal. Meanwhile, HCC patients with higher SOX9 expression show poorer prognosis [1]. Whether SOX9 is involved in sorafenib resistance in HCC is still unclear. Here, we found that sorafenib treatment increased SOX9 expression in HCC cell lines. Overexpression of exogenous SOX9 in HCC increased sorafenib resistance both in vitro and in vivo, whereas down-regulation led to inhibition of sorafenib resistance. Knock-down of SOX9 by RNA interference caused down-regulation of downstream genes, including ATP binding cassette subfamily G member 2 (ABCG2). The drug resistance to sorafenib caused by SOX9 overexpression could be ameliorated by overexpression of SOX9 in combination withby ABCG2 inhibition in HCC cell lines. In the cohort of patients resistant to sorafenib, we found that patients with lower SOX9 expression had more prolonged overall survival (OS) and progression-free survival (PFS). Cox analysis shows that SOX9 expression exerts as an independent risk factor for HCC, and logistic regression analysis reveals that SOX9 expression, tumor capsule deficiency, tumor diameters, and microvascular invasion are risk factors for poor prognosis of HCC patients. These findings demonstrate that SOX9 enhances sorafenib resistance and may regulate this process by modulating ABCG2 expression.
2020-01-13 | GSE143477 | 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-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: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:Genes specific to Sox9+ pancreatic progenitors were identified by comparing the gene expression in embryonic and adult Sox9+ cells. We used microarray analysis to detail the global changes in gene expression as Sox9 positive embryonic pancreatic progenitors differentiatiate into adult ductal cells or the endocrine lineage.
2012-08-02 | GSE34060 | GEO
Project description:SOX9 is a master transcription factor that regulates development and stem cell programs. However, its potential oncogenic activity and regulatory mechanisms that control SOX9 protein stability are poorly understood. Here we show that SOX9 is a substrate of FBW7, a tumor suppressor and a SCF (Skp1-Cul1-F-box)-type ubiquitin ligase. FBW7 recognizes a conserved degron surrounding threonine 236 (T236) in SOX9 that is phosphorylated by GSK3 kinase. Specifically, FBW7-alpha targets T236-phosphorylated SOX9 for ubiquitylation and proteasomal degradation. Further, we demonstrate that FBW7 inactivation stabilizes SOX9 protein promoting migration, metastasis and treatment resistance in medulloblastoma, one of the most common childhood brain tumors. Notably, expression of mutationally stabilized SOX9-T236/240A in medulloblastoma cells coincides with activation of pro-metastatic genes. FBW7 is frequently downregulated in all medulloblastoma subgroups and mutated specifically in SHH-driven medulloblastoma. In cases where FBW7 mRNA levels are low, SOX9 protein is significantly elevated and this phenotype is associated with metastasis at diagnosis and poor patient outcome. Finally, pharmacological inhibition of PI3K/Akt/mTOR activity destabilizes SOX9 in a GSK3/FBW7-dependent manner, rendering medulloblastoma cells sensitive to cytostatic treatment.
2016-09-13 | GSE84320 | GEO