Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Effects of SOX9 Downregulation on the Transcriptomic Landscape of Pancreatic Ductal Adenocarcinoma Cells

ABSTRACT: SOX9 is recognized as a crucial master regulator of gene transcription, playing a significant role in the developmental and differentiation processes of tissue and organ formation, particularly in the pancreas. Its overexpression has been associated with various tumors, including pancreatic cancer, and is often discussed as a potential prognostic marker. In this study, we conducted SOX9 knockdown in Colo375 and PANC-1 cell lines using RNA interference, followed by comprehensive transcriptome analysis of the transfected cells. We performed gene annotation and pathway analysis, as well as examined gene signatures related to survival and chemoresistance in pancreatic cancer within the transcriptomes of siSOX9 transfected cells. Notable differences were observed between the transcriptomes of SOX9 knockdown and control cells, including the activation of signaling pathways, differentiation processes, transcription, and methylation, alongside a reduction in the expression of genes associated with the cell cycle and apoptosis. The analysis revealed alterations in transcription factors, differentially expressed genes, oncogenes, tumor suppressor genes, genes related to epithelial-mesenchymal transition, drug resistance, and those included in prognostic signatures for pancreatic cancer in the SOX9 knockdown cells. The findings suggest that SOX9 may not serve as a reliable prognostic marker in pancreatic cancer.

ORGANISM(S): Homo sapiens

PROVIDER: GSE287340 | GEO | 2025/04/02

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Transcriptome sequencing of A549 cells

Project description:We analyzed the global effect of SOX9 knockdown and TGFB1 treatment by sequencing the transcriptomes of A549 cells transfected with siSOX9 or control siRNA and treated with TGFB1.

2024-01-15 | GSE217880 | GEO

Exocrine and connective tissue signatures in early pancreatic adenocarcinoma foci and their surrounding tissue

Project description:This project is reporting on microdissection proteomics of human operable, non-neoadjuvant treated pancreatic ductal adenocarcinomas (PDAC) with deep coverage of histologically neoplastic and adjacent healthier exocrine glands as well as stromal regions surrounding both. Through proteomic analysis, the parenchymal sample types differed significantly, with the malignant regions characterized by a broad downregulation of digestive enzymes. Instead, the stromal areas were alike, dominated by extracellular matrix proteins and lower expression of most metabolic pathways compared to the exocrine areas. Cholesterol synthesizing enzymes were more abundant in the tumor than stroma, as confirmed by an independent PDAC dataset and immunohistochemistry of PDAC microarrays. However, this was not accompanied by intratumor lipid deposition. Pathways most prognostic for survival were unexpectedly enriched in the histologically healthier exocrine glands, with a specific prognostic marker. Systematic analysis of pancreatic cancer transcriptomes from The Cancer Genome Atlas revealed that increased transcriptional complexity confers poor prognosis in PDAC.

2022-09-05 | PXD026371 | Pride

Sox9 determines translational capacity during early chondrogenic differentiation of ATDC5 cells by regulating expression of ribosome biogenesis factors and ribosomal proteins

Project description:Introduction: In addition to the well-known cartilage extracellular matrix-related expression of Sox9, we demonstrated that chondrogenic differentiation of progenitor cells is driven by a sharply defined bi-phasic expression of Sox9: an immediate early and a late (extracellular matrix associated) phase expression. In this study we aimed to determine what biological processes are driven by Sox9 during this early phase of chondrogenic differentiation. Materials: Sox9 expression in ATDC5 cells was knocked-down by siRNA transfection at the day before chondrogenic differentiation or at day 6 of differentiation. Samples were harvested at 2 hours, and 7 days of differentiation. The transcriptomes (RNA-seq approach) and proteomes (Label-free proteomics approach) were compared using pathway and network analyses. Total protein translational capacity was evaluated with the SuNSET assay, active ribosomes with polysome profiling and ribosome modus with bicistronic reporter assays. Results: Early Sox9 knockdown severely inhibited chondrogenic differentiation weeks later. Sox9 expression during the immediate early phase of ATDC5 chondrogenic differentiation regulated the expression of ribosome biogenesis factors and ribosomal protein subunits. This was accompanied by decreased translational capacity following Sox9 knockdown, and this correlated to lower amounts of active mono- and polysomes. Moreover, cap- versus IRES-mediated translation was altered by Sox9 knockdown. Sox9 overexpression was able to induce reciprocal effects to the Sox9 knockdown. Conclusion: Here we identified an essential new function for Sox9 during early chondrogenic differentiation. A role for Sox9 in regulation of ribosome amount, activity and/or composition may be crucial in preparation for the demanding proliferative phase and subsequent cartilage extracellular matrix-production of chondroprogenitors in the growth plate in vivo.

2021-06-18 | PXD024715 | Pride

Expression data in the human pancreatic cancer cell line RWP-1 subjected to SOX9 silencing

Project description:The developmental transcription factor SOX9 exerts an oncogenic activity in pancreatic cancer. We used microarrays to detail the global programme of gene expression underlying the oncogenic activity of SOX9 in pancreatic cancer.

2022-01-11 | GSE193406 | GEO

SOX9 modulates cancer biomarker and cilia genes in pancreatic cancer

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

Expression data from SOX9 overexpressing EndoC-ßH1 cells

Project description:Human ß cell dedifferentiation as a potent mechanism of diabetes is gaining prominence. Several data suggest an upregulation of the transcription factor SOX9, a progenitor and duct cell marker during ß cell dedifferentiation. However, its targets in such cells need more understanding. Here, we overexpressed SOX9 and a constitutively active mutant (VP16-SOX9∆TAD) in Human pancreatic beta EndoC-ßH1 cells in order to understand its targets.

2018-01-31 | GSE104195 | GEO

Transcriptional co-factor Transducin beta-like (TBL) 1 acts as a checkpoint in pancreatic cancer malignancy

Project description:Pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of cancer fatalities in Western societies, characterized by high metastatic potential and resistance to chemotherapy. Critical molecular mechanisms of these phenotypical features still remain unknown, thus hampering the development of effective prognostic and therapeutic measures in PDAC. Here we show that transcriptional co-factor Transducin beta-like (TBL) 1 was over-expressed in both human and murine PDAC. Inactivation of TBL1 in human and mouse pancreatic cancer cells reduced cellular proliferation and enhanced chemosensitivity, correlating with diminished glucose uptake, glycolytic flux, and PI3kinase signaling. TBL1 deficiency both prevented and reversed pancreatic tumor growth in mice, triggering transcriptional PI3kinase inhibition also in vivo. As TBL1 mRNA levels were also found to correlate with overall and disease-free survival in a cohort of human PDAC patients and to predict therapy responsiveness in these subjects, TBL1 expression may serve both as a novel prognostic marker and molecular target in the treatment of human PDAC. Capan-1 cells were transfected with control-siRNA (#1027292, Qiagen) or siRNA against human TBL1 (SI04329514, Qiagen) and RNA was isolated 24h later

2015-06-16 | E-GEOD-59761 | biostudies-arrayexpress

SOX9 targets in hESC-derived pancreatic progenitors

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

Chromatin profiling of A549 cells

Project description:We analyzed SOX9 chromatin binding upon TGFB1 treatment as well as the global effect of SOX9 knockdown and TGFB1 treatment by ChIP-sequencing and ATAC-sequencing of A549 cells transfected with siSOX9 or control siRNA and treated with TGFB1.

2024-07-01 | GSE252848 | GEO

ZXDC is highest expressed transcription factor on TBLR1-overexpressed HeLa cells

Project description:In our previous study, we revealed that transducing (beta)-like 1X-linked (TBLR1) is a potential prognostic marker which has a negative effect on the overall survival in cervical cancer patients.This transcriptome sequencing results of TBLR1-overexpressing and TBLR1-knockdown cervical cells identified ZXDC (ZXD family zinc finger C) as the most significantly differently expressed transcription factor (TF) among all TFs (Figure S1), indicating its potential role in cervical cancer progression.

2023-06-13 | GSE234087 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data