RNAseq highlights the role of Sirt2 in protecting neuronal cell from cisplatin-treated injury
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB36706 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| ERR3892740.fastq.gz | Fastqsanger.gz | |||
| ERR3892750.fastq.gz | Fastqsanger.gz | |||
| ERR3892741.fastq.gz | Fastqsanger.gz | |||
| ERR3892751.fastq.gz | Fastqsanger.gz | |||
| ERR3892742.fastq.gz | Fastqsanger.gz |
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Project description:We provide evidence for the essential role of Sirt2 in IFN mediated signaling. Our studies demonstrate that SIRT2 controls expression of key interferon stimulated genes (ISGs) that mediate important biological functions, including anti-viral and antineoplastic responses.
2015-12-31 | GSE66033 | GEO
Project description:Metabolism is a key driver of T cell functions, and the switch from oxidative-phosphorylation to aerobic glycolysis is a hallmark of T cell activation. However, the mechanisms underlying the metabolic switch remain unclear. Here, we report that the Sirtuin-2 (Sirt2) deacetylase protein functions as a metabolic checkpoint that harnesses T cell effector functions and impairs anti-tumor immunity. Specifically, upregulation of Sirt2 expression in human tumor-infiltrating T lymphocytes (TILs) negatively correlates with response to Nivolumab and TIL therapy in non-small cell lung cancer. Mechanistically, Sirt2 suppresses aerobic glycolysis by deacetylating key glycolytic enzymes. Accordingly, Sirt2-deficient T cells manifest increased glycolysis, display enhanced proliferation and effector functions, and have superior anti-tumor activity. Importantly, pharmacologic inhibition of Sirt2 endows human TILs with these superior metabolic fitness and enhanced effector functions. These findings indicate Sirt2 as an actionable target for reprogramming T cell metabolism to augment a broad spectrum of cancer immunotherapies.
2020-09-16 | GSE151421 | GEO
Project description:In order to explore the effects of SIRT2 on the liver metabolic function of mice under metabolic stress, we constructed SIRT2 knockout mice.
2023-04-08 | GSE229161 | GEO
Project description:tissue culture cells were treated with an inhibitor to the deacetylase SIRT2 (AGK2) and infected with Listeria monocytogenes
2013-06-01 | E-MEXP-3912 | biostudies-arrayexpress
Project description:BACKGROUND:Chemotherapy-induced peripheral neuropathy is not only one of the most common causes of dose reduction or discontinuation of cancer treatment, but it can also permanently decrease the quality of life of cancer patients and survivors. Notably, Sirt2 protects many organs from various injuries, including diabetic peripheral neuropathy. As demonstrated previously by our laboratory and others, the overexpression of Sirt2 can improve cisplatin-induced neuropathy, although the mechanism is still unclear. RESULTS:In this study, the underlying mechanism by which Sirt2 protects neurons from cisplatin-induced injury was explored using the RNAseq technique in cultured rodent neurons. Sirt2 status was modified by genetic knockout (Sirt2/KO) and was then reconstituted in Sirt2/KO cells (Sirt2/Res). We observed 323 upregulated genes and 277 downregulated genes in Sirt2-expressing cells (Sirt2/Res) compared to Sirt2-deficient cells (Sirt2/KO). Pathway analysis suggested that Sirt2 may affect several pathways, such as MAPK, TNF, and cytokine-cytokine interaction. Furthermore, cisplatin-induced changes to the transcriptome are strongly associated with Sirt2 status. Cisplatin induced distinctive transcriptome changes for 227 genes in Sirt2-expressing cells and for 783 genes in Sirt2-deficient cells, while changes in only 138 of these genes were independent of Sirt2 status. Interestingly, changes in the p53 pathway, ECM-receptor interactions, and cytokine-cytokine receptor interactions were induced by cisplatin only in Sirt2-deficient cells. CONCLUSIONS:This study demonstrated that Sirt2 regulates the transcriptome in cultured rodent neuronal cells. Furthermore, Sirt2-associated transcriptome regulation may be an important mechanism underlying the role of Sirt2 in organ protection, such as in cisplatin-induced neuronal injury. Sirt2 may be a potential target for the prevention and treatment of chemotherapy-induced neuropathy.
| S-EPMC7053098 | biostudies-literature
Project description:Aberrant expression of IL-17A together with abated IL-2 production by effector CD4+ T cells contributes to the pathogenesis of systemic lupus erythematosus (SLE). Here we report that Sirtuin 2 (SIRT2), a member of the family of NAD+-dependent histone deacetylases, suppresses IL-2 production by CD4+ T cells while it promotes their differentiation into Th17 cells. Mechanistically, we show that SIRT2 is responsible for the deacetylation of p70S6K and the activation of the mTORC1/HIF-1α/RORγt pathway and the generation of Th17 cells differentiation. Additionally, SIRT2 is responsible for the deacetylation of c-Jun and histones on the Il-2 gene, resulting in decreased IL-2 production. We found that the transcription factor inducible cAMP early repressor (ICER), which is overexpressed in T cells from people with SLE and lupus-prone mice, binds directly to the Sirt2 promoter and promotes its transcription. AK-7, a SIRT2 inhibitor limited the ability of adoptively transferred antigen-specific CD4+ T cells to cause autoimmune encephalomyelitis and disease in the lupus-prone MRL/lpr mice. Finally, CD4+ T cells from SLE patients exhibited increased expression of SIRT2, and pharmacological inhibition of SIRT2 in primary CD4+ T cells from patients with SLE attenuated their ability to differentiate into Th17 cells and promoted IL-2–producing T cells. Collectively, these results suggest that SIRT2-mediated deacetylation is essential for the aberrant expression of IL-17A and IL-2 and that SIRT2 may be a promising molecular target for new therapies for SLE.
2022-03-30 | GSE199496 | GEO
Project description:To investigate the differentially expressed RNA levels in the liver of aged LoxP and SIRT2-KOhep mice. We then performed gene expression profiling analysis using data obtained from RNA-seq of liver of aged LoxP and SIRT2-KOhep mice
2023-04-30 | GSE228204 | GEO
Project description:Growing evidence indicates that metabolism is a key driver of T cell functions. A switch from oxidative phosphorylation to aerobic glycolysis is a hallmark of T cell activation and is required to meet metabolic demands of proliferation and effector functions. However, the mechanisms underlying the metabolic switch in T cells remain unclear. Here, we identify Sirt2 as a crucial immune checkpoint coordinating metabolic and functional fitness of T cells. Sirt2 is induced upon T cell activation and increases in late maturation stages. Sirt2 negatively regulates glycolysis by targeting key glycolytic enzymes. Remarkably, Sirt2 knockout T cells exhibit profound upregulation of aerobic glycolysis with enhanced proliferation and effector function and thus effectively reject tumor challenge in vivo. Furthermore, pharmacologic inhibition of Sirt2 in human tumor infiltrating lymphocytes demonstrated a similar phenotype. Taken together, our results demonstrate Sirt2 as an actionable target to reprogram T cell metabolism to augment immunotherapy.
2020-06-15 | PXD012811 | Pride
Project description:Growing evidence indicates that metabolism is a key driver of T cell functions. A switch from oxidative phosphorylation to aerobic glycolysis is a hallmark of T cell activation and is required to meet metabolic demands of proliferation and effector functions. However, the mechanisms underlying the metabolic switch in T cells remain unclear. Here, we identify Sirt2 as a crucial immune checkpoint coordinating metabolic and functional fitness of T cells. Sirt2 is induced upon T cell activation and increases in late maturation stages. Sirt2 negatively regulates glycolysis by targeting key glycolytic enzymes. Remarkably, Sirt2 knockout T cells exhibit profound upregulation of aerobic glycolysis with enhanced proliferation and effector function and thus effectively reject tumor challenge in vivo. Furthermore, pharmacologic inhibition of Sirt2 in human tumor infiltrating lymphocytes demonstrated a similar phenotype. Taken together, our results demonstrate Sirt2 as an actionable target to reprogram T cell metabolism to augment immunotherapy.
2020-07-03 | PXD020150 | Pride
Project description:The NAD+ dependent deacetylase enzyme SIRT2 functions in diverse cellular processes including the cell cycle, metabolism and has recently been demonstrated to have important roles during tumorigenesis and bacterial infection. Though predominantly localised in the cytoplasm SIRT2 has been shown to continuously cycle in and out of the nucleus where it functions as a histone deacetylase. To investigate the varied and pleiotropic nature of SIRT2 we performed proteomic analyses using liquid chromatography-tandem mass spectrometry to identify novel interacting partners. Using this approach, we have generated a whole cell interactome consisting of over 500 proteins highlighting the distinct cellular processes in which SIRT2 functions.
2020-02-20 | PXD011523 | Pride