DYRK1B Overexpression Promotes Senescence-Like Transcriptional and Secretory Programs in A549 Lung Cancer Cells
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE326699 | GEO | 2026/04/01
REPOSITORIES: GEO
Similar Datasets
Project description:DYRK1B Overexpression Promotes Senescence-Like Transcriptional and Secretory Programs in A549 Lung Cancer Cells
| PRJNA1446780 | ENA
Project description:Illuminating the mechanisms controlling glucose homeostasis may deepen our understanding of the pathogenesis of T2DM and provide new therapeutic strategies for T2DM in future. As reported, Dyrk1b is a pleiotropic protein and its genetic mutations associate with blood glucose levels. Yet, the role of Dyrk1b in glucose metabolism is not well understood. Herein, we find that hepatic Dyrk1b overexpression in mice impairs the glucose tolerance and insulin resistance, whereas global Dyrk1b deficiency improves glucose metabolism of mcie. Dyrk1b overexpression in vitro blunts insulin signalling and glucose uptake. Collectively, our study uncovers a novel link between hepatic Dyrk1b and whole body glucose homeostasis.
2025-05-29 | GSE234405 | GEO
Project description:One of the causes of hyperglycemia in type 2 diabetes is elevated hepatic glucose production. AKT-FOXO1 pathway is primarily involved in the hormonal upregulation of this process, and pharmacological or genetic inhibition of this pathway prevents diabetes in animal models. Here we report that DYRK1B regulates FoxO1 function through phosphorylation to regulate hepatic glucose metabolism. DYRK1B expression is induced by fasting and in diabetic mice. DYRK1B promoted hepatic gluconeogenesis and glucose intolerance in in vivo and in vitro model systems. Liver-specific DYRK1B conditional knockout mice were protected from diet-induced hyperglycemia. Mechanistically, DYRK1B interacted with and phosphorylated FoxO1, primarily at T467S468, which is required for its nuclear localization. DYRK1B inhibited AKT mediated FoxO1 phosphorylation at T24 and S256 and enhanced its nuclear retention. DYRK1B mediated phosphorylation of FoxO1 enhanced the expression of gluconeogenic genes and promoted gluconeogenesis. Treatment with DYRK1B pharmacological inhibitor AZ191 significantly lowered blood glucose levels in diabetic mice. We conclude that DYRK1B is a regulator of glucose metabolism, and its pharmacological inhibition could serve as therapeutic target for treating diabetes.
2025-04-30 | GSE262106 | GEO
Project description:One of the causes of hyperglycemia in type 2 diabetes is elevated hepatic glucose production. AKT-FOXO1 pathway is primarily involved in the hormonal upregulation of this process, and pharmacological or genetic inhibition of this pathway prevents diabetes in animal models. Here we report that DYRK1B regulates FoxO1 function through phosphorylation to regulate hepatic glucose metabolism. DYRK1B expression is induced by fasting and in diabetic mice. DYRK1B promoted hepatic gluconeogenesis and glucose intolerance in in vivo and in vitro model systems. Liver-specific DYRK1B conditional knockout mice were protected from diet-induced hyperglycemia. Mechanistically, DYRK1B interacted with and phosphorylated FoxO1, primarily at T467S468, which is required for its nuclear localization. DYRK1B inhibited AKT mediated FoxO1 phosphorylation at T24 and S256 and enhanced its nuclear retention. DYRK1B mediated phosphorylation of FoxO1 enhanced the expression of gluconeogenic genes and promoted gluconeogenesis. Treatment with DYRK1B pharmacological inhibitor AZ191 significantly lowered blood glucose levels in diabetic mice. We conclude that DYRK1B is a regulator of glucose metabolism, and its pharmacological inhibition could serve as therapeutic target for treating diabetes.
2025-04-30 | GSE263028 | GEO
Project description:Elucidation of the mechanisms controlling glucose homeostasis may deepen our understanding of the pathogenesis of T2DM and provide new therapeutic strategies for T2DM in the future. As reported, Dyrk1b is a pleiotropic protein and its genetic mutations are associated with blood glucose levels. However, the role of Dyrk1b in glucose metabolism is not well understood. Herein, we find that hepatic Dyrk1b overexpression in mice impairs the glucose tolerance and insulin resistance, whereas global Dyrk1b deficiency improves glucose metabolism of mcie. Dyrk1b overexpression in vitro blunts insulin signalling and glucose uptake. Collectively, our study uncovers a novel link between hepatic Dyrk1b and whole body glucose homeostasis.
2025-08-01 | GSE237672 | GEO
Project description:Illuminating the mechanisms controlling glucose homeostasis may deepen our understanding of the pathogenesis of T2DM and provide new therapeutic strategies for T2DM in future. As reported, Dyrk1b is a pleiotropic protein and its genetic mutations associate with blood glucose levels. Yet, its role in glucose metabolism remains to be established. Herein, we invetigate the role of Dyrk1b in glucose metabolism and the underlying mechanisms. We find that hepatic Dyrk1b overexpression in mice impairs the glucose tolerance and insulin resistance, whereas global Dyrk1b deficiency improves glucose metabolism of mcie. Dyrk1b overexpression in vitro blunts insulin signalling and glucose uptake. Quantitative proteomic analyses further reveal that Wbp2 is a putative target of Dyrk1b. Importantly, hepatic Wbp2 restoration rescues the glucose homeostasis in Dyrk1b overexpression mice. Additionally, ATAC-seq analyses indicate Dyrk1b’s role in remodelling hepatic chromatin landscape. Collectively, our study uncovers a novel link between hepatic Dyrk1b and whole body glucose homeostasis via modulation of hepatic Wbp2 expression.
2025-05-29 | GSE234275 | GEO
Project description:Here, we investigates the effects of dual-specificity tyrosine-regulated kinase 1B (DYRK1B) on mitochondrial bioenergetics, cardiac hypertrophy, and heart failure.We engineered DYRK1B transgenic and the effects of DYRK1B and its downstream mediators were subsequently elucidated using RNA-seq analysis. In this dataset, we inquire the transcriptional profile of WT and DYRK1B transgenic hearts at 3-day and 8-week old.
2021-09-19 | GSE184155 | GEO
Project description:Lung cancer cell line, A549 cells, was transfected with siPML or siCtrl for 48hr to knockdown PML expression. WDR4 or vector was overexpressed in A549 cells for 48hr. These four sets of cells were then subjected to microarray profiling using the Human OneArray microarray (version HOA6.1, GEO Platform GPL19137) from Phalanx Biotech Group. Comparison of transcriptomes from siPML/siCtrl and W4/vec in A549 cells
2016-07-04 | E-GEOD-83499 | biostudies-arrayexpress
Project description:Anticancer drug sagopilone in lung cancer line A549. We performed gene expression analysis of lung cancer cell line A549 treated with sagopilone and paclitaxel. The aim was to analyse gene expression differences between the two drugs in two different concentrations. A549 cells were treated with medium containing either 2.5 nM sagopilone, 40 nM sagopilone, 4 nM paclitaxel or 40 nM paclitaxel, respectively, vehicle (ethanol 0.1%), or were left untreated for 18 hours. The two different concentrations were chosen according the phenotypes they have caused in A549 cells. Treatment with 2.5 nM sagopilone, 4 nM paclitaxel induced an aneuploid cell population, whereas treatment with 40 nM sagopilone and 40 nM paclitaxel induced mitotic arrest.
2012-01-01 | E-MTAB-377 | biostudies-arrayexpress