RNA-Seq analysis SIRT1 knockdown effect on pancreatic cancer cell line
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE171118 | GEO | 2021/06/18
REPOSITORIES: GEO
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Project description:Pancreatic cancer is a common malignant tumor with poor prognosis. Accumulating evidence indicates that sirtuin 1 (SIRT1) exerts biological functions in various cancers.SIRT1 plays an important role in tumorigenesis, development, and drug resistance by blocking aging and apoptosis, also promoting cell growth and angiogenesis.However, how SIRT1 functions in the development of pancreatic cancer stem cells (CSCs) is currently poorly understood. Here, we showed that SIRT1 inhibits the differentiation of cancer cells by inhibiting various genes expression , including GRHL3, thus promoting the stemness and tumorigenesis of pancreatic cancer.
2021-06-18 | GSE163101 | GEO
Project description:Sirtuin-1 (Sirt1), a class III histone/protein deacetylase is central to cellular metabolism, stress responses and aging, but its contributions to various host immune functions have been little investigated. To study the role of Sirt1 in T-cell functions, we undertook targeted deletions by mating mice with a floxed Sirt1 gene to mice expressing CD4-cre or Foxp3-cre recombinase, respectively. We found that Sirt1 deletion left conventional T-effector cell activation, proliferation and cytokine production largely unaltered. However, Sirt1 targeting promoted the expression and acetylation of Foxp3, a key transcription factor in T-regulatory (Treg) cells, and increased Treg suppressive functions in vitro and in vivo. Consistent with these data, mice with targeted deletions of Sirt1 in either CD4+ T-cells or Foxp3+ Treg cells exhibited prolonged survival of MHC-mismatched cardiac allografts. Allografts in Sirt1 targeted recipients showed long-term preservation of myocardial histology and infiltration by Foxp3+ Treg cells. Comparable results were seen in wild-type allograft recipients treated with Sirt1 inhibitors, such as EX-527 and splitomicin. Hence, Sirt1 may inhibit Treg functions and its targeting may have therapeutic value in autoimmunity and transplantation. RNA from three independent samples from magnetically separated CD4+CD25+ Treg of Sirt1 knock out, compared to wild type (C57BL6) control
2011-01-05 | E-GEOD-26425 | biostudies-arrayexpress
Project description:Sirtuin-1 (Sirt1), a class III histone/protein deacetylase is central to cellular metabolism, stress responses and aging, but its contributions to various host immune functions have been little investigated. To study the role of Sirt1 in T-cell functions, we undertook targeted deletions by mating mice with a floxed Sirt1 gene to mice expressing CD4-cre or Foxp3-cre recombinase, respectively. We found that Sirt1 deletion left conventional T-effector cell activation, proliferation and cytokine production largely unaltered. However, Sirt1 targeting promoted the expression and acetylation of Foxp3, a key transcription factor in T-regulatory (Treg) cells, and increased Treg suppressive functions in vitro and in vivo. Consistent with these data, mice with targeted deletions of Sirt1 in either CD4+ T-cells or Foxp3+ Treg cells exhibited prolonged survival of MHC-mismatched cardiac allografts. Allografts in Sirt1 targeted recipients showed long-term preservation of myocardial histology and infiltration by Foxp3+ Treg cells. Comparable results were seen in wild-type allograft recipients treated with Sirt1 inhibitors, such as EX-527 and splitomicin. Hence, Sirt1 may inhibit Treg functions and its targeting may have therapeutic value in autoimmunity and transplantation.
2011-01-05 | GSE26425 | GEO
Project description:Sterile alpha motif and HD domain-containing protein 1 (SAMHD1) has a dNTPase-independent function in promoting DNA end resection to facilitate DNA double-strand break (DSB) repair by homologous recombination (HR); however, it is not known if upstream signaling events govern this activity. Here, we show that SAMHD1 is deacetylated by the SIRT1 sirtuin deacetylase, facilitating its binding with ssDNA at DSBs, to promote DNA end resection and HR. SIRT1 complexes with and deacetylates SAMHD1 at conserved lysine 354 (K354) specifically in response to DSBs. K354 deacetylation by SIRT1 promotes DNA end resection and HR but not SAMHD1 tetramerization or dNTPase activity. Mechanistically, K354 deacetylation by SIRT1 promotes SAMHD1 recruitment to DSBs and binding to ssDNA at DSBs, which in turn facilitates CtIP ssDNA binding, leading to promotion of genome integrity. Our findings define a mechanism governing the dNTPase-independent resection function of SAMHD1 by SIRT1 deacetylation in promoting HR and genome stability.
2023-03-11 | PXD031357 | Pride
Project description:Sirtuin 1 (Sirt1) has been reported to be a critical positive regulator of glucose-stimulated insulin secretion in pancreatic beta-cells. The effects on islet cells and blood glucose levels when Sirt1 is deleted specifically in the pancreas are still unclear.This study examined islet glucose responsiveness, blood glucose levels, pancreatic islet histology and gene expression in Pdx1-Cre;Sirt1(ex4F/F) mice that have loss of function and loss of expression of Sirt1 specifically in the pancreas. We found that in the Pdx1-Cre;Sirt1(ex4F/F) mice, the relative insulin positive area and the islet size distribution were unchanged. However, beta-cells were functionally impaired, presenting with lower glucose-stimulated insulin secretion. This defect was not due to a reduced expression of insulin but was associated with a decreased expression of the glucose transporter Slc2A2/Glut2 and of the Glucagon like peptide-1 receptor (Glp1r) as well as with a marked down regulation of endoplasmic reticulum (ER) chaperones that participate in the Unfolded Protein Response (UPR) pathway. Counter intuitively, the Sirt1-deficient mice did not develop hyperglycemia. Pancreatic polypeptide (PP) cells were the only other islet cells affected, with reduced numbers in the Sirt1-deficient pancreas. This study provides new mechanistic insights showing that beta-cell function in Sirt1-deficient pancreas is affected due to altered glucose sensing and deregulation of the UPR pathway. Interestingly, we uncover a context in which impaired beta-cell function is not accompanied by increased glycemia. This points to a unique compensatory mechanism. Given the reduction in PP, investigation of its role in the control of blood glucose is warranted. To uncover other Sirt1-regulated mechanisms, we performed a gene expression microarray analysis comparing pancreata from the 6 month old Sirt1âdeficient mice to their controls (n=3 per group).
2016-03-01 | E-GEOD-67239 | biostudies-arrayexpress
Project description:We demonstrate that Sirtuin 1 (SIRT1) is an indispensable age-related regulator of invasion and spacing of blastocysts, as well as decidualization of stromal cells. Here, we report the sequencing of the uterine transcriptome of control and conditional knock-out of the Sirtuin 1 (SIRT1) at day 3.5 of murine pregnancy.
2022-09-14 | GSE186065 | GEO
Project description:The goal of this project is to investigate the role of SIRT1, the most conserved mammalian NAD+-dependent protein deacetylase, in the regulation of heart development. SIRT1 is important for heart development and functions. However, the underlying molecular mechanisms remain undefined. In this study, we analyzed the gene expression profiles in E18.5 WT and SIRT1 KO mouse hearts.
2021-08-23 | GSE86835 | GEO
Project description:Sirtuin 1 (Sirt1) has been reported to be a critical positive regulator of glucose-stimulated insulin secretion in pancreatic beta-cells. The effects on islet cells and blood glucose levels when Sirt1 is deleted specifically in the pancreas are still unclear.This study examined islet glucose responsiveness, blood glucose levels, pancreatic islet histology and gene expression in Pdx1-Cre;Sirt1(ex4F/F) mice that have loss of function and loss of expression of Sirt1 specifically in the pancreas. We found that in the Pdx1-Cre;Sirt1(ex4F/F) mice, the relative insulin positive area and the islet size distribution were unchanged. However, beta-cells were functionally impaired, presenting with lower glucose-stimulated insulin secretion. This defect was not due to a reduced expression of insulin but was associated with a decreased expression of the glucose transporter Slc2A2/Glut2 and of the Glucagon like peptide-1 receptor (Glp1r) as well as with a marked down regulation of endoplasmic reticulum (ER) chaperones that participate in the Unfolded Protein Response (UPR) pathway. Counter intuitively, the Sirt1-deficient mice did not develop hyperglycemia. Pancreatic polypeptide (PP) cells were the only other islet cells affected, with reduced numbers in the Sirt1-deficient pancreas. This study provides new mechanistic insights showing that beta-cell function in Sirt1-deficient pancreas is affected due to altered glucose sensing and deregulation of the UPR pathway. Interestingly, we uncover a context in which impaired beta-cell function is not accompanied by increased glycemia. This points to a unique compensatory mechanism. Given the reduction in PP, investigation of its role in the control of blood glucose is warranted.
2016-03-01 | GSE67239 | GEO
Project description:A longevity gene, sirtuin 1 (SIRT1) and energy sensor AMP-activated protein kinase (AMPK) have common activators such as caloric restriction, oxidative stress and exercise.The objective is to characterize the role of cardiomyocyte SIRT1 in age-related impaired ischemic AMPK activation and increased susceptibility to ischemic insults.
2017-05-11 | GSE98749 | GEO
Project description:Pancreatic cancer stem cells (CSCs) have been described as CD24+/CD44+/EpCAM+ or CD133+ cells. However, no study has determined the co-expression of all of these markers in pancreatic ductal adenocarcinoma. Similarly to other combinations of CSC markers, CD24+/ CD44+/EpCAM+/CD133+ phenotype might more accurately identify true pancreatic CSCs. Therefore, we performed a detailed co-expression analysis of CD24, CD44, EpCAM, and CD133 in 3 cell lines derived from primary pancreatic ductal adenocarcinomas (PDACs). Gene expression profiling was applied in order to further investigate the observed differences in proportion of cells that co-expressed CSC markers among the cell lines.
2016-02-29 | E-MTAB-4055 | biostudies-arrayexpress