Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression [Mice]

ABSTRACT: Oral Squamous Cell Carcinoma (OSCC) is a type of cancer that arises from preneoplastic precursors, which undergo genetic and epigenetic modifications. Lysine-specific demethylase 1 (LSD1) is a key OSCC promoter. LSD1 knockout or pharmacological inhibition in mouse OSCC reversed OSCC preneoplasia in our study. LSD1 inhibition attenuated the cell cycle, immunosuppression and promoted the infiltration of CD45+, TCRß+, CD4+, and CD8+ cells. Next, we tested the clinical candidate LSD1 inhibitor (Seclidemstat) in feline clinically spontaneous natural OSCC and found that it was safe and attenuated the STAT3 network. Mechanistic studies have shown that LSD1 reprograms preneoplasia to promote STAT3 signaling, cell cycle mediator CDK7, and immunosuppressive CTLA4 to OSCC progression. Interestingly, we found that the LSD1 inhibitor (SP2509) attenuated cyclin-dependent kinase 7 (CDK7) phosphorylation at T170 and eukaryotic initiation factor 4 B (Eif4B) phosphorylation at S422. We identified a new mechanism in OSCC preneoplasia that LSD1 promotes STAT3 mediated by CDK7 phosphorylation, leading to overall changes in the tumor microenvironment, leading to immunosuppression and progression to OSCC, which could have applications for understanding the mechanism as well as design strategies to control the progression of preneoplasia to OSCC.

ORGANISM(S): Mus musculus

PROVIDER: GSE277935 | GEO | 2025/04/23

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression [Feline]

Project description:Oral Squamous Cell Carcinoma (OSCC) is a type of cancer that arises from preneoplastic precursors, which undergo genetic and epigenetic modifications. Lysine-specific demethylase 1 (LSD1) is a key OSCC promoter. LSD1 knockout or pharmacological inhibition in mouse OSCC reversed OSCC preneoplasia in our study. LSD1 inhibition attenuated the cell cycle, immunosuppression and promoted the infiltration of CD45+, TCRß+, CD4+, and CD8+ cells. Next, we tested the clinical candidate LSD1 inhibitor (Seclidemstat) in feline clinically spontaneous natural OSCC and found that it was safe and attenuated the STAT3 network. Mechanistic studies have shown that LSD1 reprograms preneoplasia to promote STAT3 signaling, cell cycle mediator CDK7, and immunosuppressive CTLA4 to OSCC progression. Interestingly, we found that the LSD1 inhibitor (SP2509) attenuated cyclin-dependent kinase 7 (CDK7) phosphorylation at T170 and eukaryotic initiation factor 4 B (Eif4B) phosphorylation at S422. We identified a new mechanism in OSCC preneoplasia that LSD1 promotes STAT3 mediated by CDK7 phosphorylation, leading to overall changes in the tumor microenvironment, leading to immunosuppression and progression to OSCC, which could have applications for understanding the mechanism as well as design strategies to control the progression of preneoplasia to OSCC.

2025-04-23 | GSE277930 | GEO

Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression [Mice]

Project description:Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression [Mice]

| PRJNA1164775 | ENA

Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression [Feline]

Project description:Lysine-specific demethylase 1 controls key OSCC preneoplasia inducer STAT3 through CDK7 phosphorylation during oncogenic progression and immunosuppression [Feline]

| PRJNA1164764 | ENA

RNF20 contributes to epigenetic immunosuppression through CDK9-dependent LSD1 stablization (ChIP-Seq)

Project description:Cyclin-dependent kinase 9 (CDK9) plays a critical role in transcription initiation and is essential for maintaining gene silencing at heterochromatic loci. Inhibition of CDK9 increases sensitivity to immunotherapy, but the underlying mechanism remains unclear. We now report that RNF20 stabilizes LSD1 via K29-mediated ubiquitination, which is dependent on CDK9-mediated phosphorylation. This CDK9- and RNF20-dependent LSD1 stabilization is necessary for the demethylation of histone H3K4, then subsequent repression of endogenous retrovirus (ERVs), and an interferon response, leading to epigenetic immunosuppression. Moreover, we found that loss of RNF20 sensitizes cancer cells to the immune checkpoint inhibitor anti-PD-1 in vivo, and that this effect can be rescued by the expression of ectopic LSD1. Our findings are supported by the observation that RNF20 levels correlate with LSD1 levels in human breast cancer specimens. This study sheds light on the role of RNF20 in CDK9-dependent LSD1 stabilization, which is crucial for epigenetic silencing and immunosuppression. Our findings explore the potential importance of targeting the CDK9-RNF20-LSD1 axis in the development of new cancer therapies.

2024-01-18 | GSE247306 | GEO

RNF20 contributes to epigenetic immunosuppression through CDK9-dependent LSD1 stablization (RNA-Seq)

2024-01-18 | GSE247307 | GEO

Opposing Roles of STAT1 and STAT3 in IL-21 Function in CD4+ T cells

Project description:Interleukin-21 (IL-21) is a type 1 cytokine essential for immune cell differentiation and function. Although IL-21 can activate several STAT family transcription factors, previous studies focused mainly on the role of STAT3 in IL-21 signaling. Here, we investigated the role of STAT1 and show that STAT1 and STAT3 have at least partially opposing roles in IL-21 signaling in CD4+ T cells. IL-21 induced STAT1 phosphorylation, and this was augmented in Stat3-deficient CD4+ T cells. RNA-Seq analysis of CD4+ T cells from Stat1- and Stat3-deficient mice revealed that both STAT1 and STAT3 are critical for IL-21-mediated gene regulation. Expression of some genes, including Tbx21 and Ifng, was differentially regulated by STAT1 and STAT3, and interestingly, ChIP-Seq analysis showed that STAT3 binding at Tbx21 and Ifng loci was attenuated in Stat1-deficient cells. Moreover, opposing actions of STAT1 and STAT3 on IFN- expression in CD4+ T cells were demonstrated in vivo during chronic lymphocytic choriomeningitis (LCMV) infection. Finally, IL-21-mediated induction of STAT1 phosphorylation, as well as IFNG and TBX21 expression, were higher in CD4+ T cells from patients with autosomal dominant hyper-IgE syndrome (AD-HIES), which is caused by STAT3 deficiency. These data indicate an interplay between STAT1 and STAT3 in fine-tuning IL-21 actions. Genome-wide transcription factors mapping and binding of STAT3 in mouse CD4+ T cells in both WT and Stat1-deficient mice. RNA-Seq is performed in mouse CD4+ T cells in WT, Stat1-deficient and Stat3-deficient mice.

2015-07-01 | E-GEOD-63204 | biostudies-arrayexpress

Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

Project description:Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features

| PRJNA714945 | ENA

Expression data transgenic mouse mammary tumors

Project description:Immunosurveillance constitutes the first step of cancer immunoediting in which developing malignant lesions are eliminated by anti-tumorigenic immune cells. However, the mechanisms by which neoplastic cells induce an immunosuppressive state to evade the immune response are still unclear. The transcription factor Stat3 has been implicated in breast carcinogenesis and tumor immunosuppression in advanced disease, but its involvement in early disease development has not been established. Here, we genetically ablated Stat3 in the tumor epithelia of the inducible PyVmT mammary tumor model and found that Stat3-deficient mice recapitulated the three phases of immunoediting: elimination, equilibrium, and escape. Pathological analyses revealed that Stat3-deficient mice initially formed hyperplastic and early adenoma-like lesions that later completely regressed, thereby preventing the emergence of mammary tumors in the majority of animals. Furthermore, tumor regression was correlated with massive immune infiltration into the Stat3-deficient lesions, leading to their elimination. In a minority of animals, focal, non-metastatic Stat3-deficient mammary tumors escaped immunosurveillance after a long latency or equilibrium period. Taken together, our findings suggest that tumor epithelial expression of Stat3 plays a critical role in promoting an immunosuppressive tumor microenvironment during breast tumor initiation and progression, and prompt further investigation of Stat3 inhibitory strategies that may reactivate the immunosurveillance program. We used microarrays to detail determine the transcriptional difference between PyVmT-driven mouse mammary tumors that progressed in the presence or absense of epithelial Stat3. Mammary tumors from transgenic mice were excise and flash frozen. Tumors were analyzed from 8 Stat3-proficient tumors and 6 Stat3-deficient tumors. RNA was extracted and hybridization on Affymetrix microarrays.

2015-11-25 | E-GEOD-75325 | biostudies-arrayexpress

Opposing Roles of STAT1 and STAT3 in IL-21 Function in CD4+ T cells

2015-07-01 | GSE63204 | GEO

CDK7 kinase activity promotes RNA polymerase II promoter escape by facilitating initiation factor release

Project description:Cyclin-dependent kinase 7 (CDK7), part of the general transcription factor TFIIH, promotes gene transcription by phosphorylating the C-terminal domain of RNA polymerase II (RNA Pol II). Here, we combine rapid CDK7 kinase inhibition with multi-omics analysis to unravel the direct functions of CDK7 in human cells. CDK7 inhibition causes RNA Pol II retention at promoters, leading to decreased RNA Pol II initiation and immediate global downregulation of transcript synthesis. Elongation, termination, and recruitment of co-transcriptional factors are not directly affected. Although RNA Pol II, initiation factors, and Mediator accumulate at promoters, RNA Pol II complexes can also proceed into gene bodies without promoter-proximal pausing while retaining initiation factors and Mediator. Further downstream, RNA Pol II phosphorylation increases and initiation factors and Mediator are released, allowing recruitment of elongation factors and an increase in RNA Pol II elongation velocity. Collectively, CDK7 kinase activity promotes the release of initiation factors and Mediator from RNA Pol II, facilitating RNA Pol II escape from the promoter.

2024-05-31 | PXD037842 | Pride

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