Similar Datasets
Project description:RNA-seq following JunD depletion
| PRJNA474228 | ENA
Project description:Cigarette smoke (CS)-induced airway inflammation is an important pathologic feature of chronic obstructive pulmonary disease (COPD). Recent studies suggest a potential role of JunD in the regulation of inflammation, but its role in CS-induced airway inflammation has not been reported. This study aimed to determine its role in CS-induced airway inflammation through bioinformatics analysis and in vitro and in vivo experiments. Data from the Gene Expression Omnibus (GEO) database (GSE37147) were analyzed using weighted gene co-expression network analysis (WGCNA) and key driver analysis (KDA), and these analyses were validated using the GSE47460 dataset. The effect of CS on JunD expression was examined in lung tissues of COPD patients and CS-exposed mice and in CS extract (CSE)-exposed BEAS-2B cells. The effects of CSE on airway epithelial inflammatory injury after JunD knockdown or overexpression were also investigated. mRNA-seq and chromatin immunoprecipitation (ChIP)-seq were used to explore the mechanism of JunD-mediated CS-induced airway inflammation. Mice were injected with adeno-associated virus serotype 9 (AAV9)-JunD vector or control vector and then exposed to CS for 4 weeks, and lung tissue morphology and airway inflammation were evaluated. KDA of the lung function-related gene modules in GSE37147 revealed a potential role of JunD in COPD, which was validated in GSE47460. JunD was downregulated in lung tissues of COPD patients and CS-exposed mice and in BEAS-2B cells. JunD knockdown aggravated CSE-induced tumor necrosis factor (TNF)-α and interleukin (IL)-1β release by BEAS-2B cells, while JunD overexpression attenuated these effects. mRNA-seq and ChIP-seq identified several JunD-regulated genes, which are involved in the immune response and TNF signaling pathway and are commonly dysregulated in cell models of airway inflammation. In vivo, JunD overexpression attenuated the CS-induced inflammatory cell infiltration and inflammatory cytokine release in mouse lungs. Thus, JunD is involved in CS-induced airway inflammation and JunD-based therapy may be useful in CS-induced airway disorders.
2020-12-09 | GSE162902 | GEO
Project description:Background: MLL-rearranged (MLLr) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) involve reciprocal oncogenic translocations of the KMT2A/KMT2B (MLL1/MLL2) gene on chromosome 11q23 with various translocation partner genes, which yields to chimeric MLL fusion proteins (MLL-FPs). Menin, the protein product of the MEN1 gene, is essential for the leukemogenic activity of MLL-FPs. Revumenib, a small-molecule inhibitor that selectively disrupts the menin-MLL interaction, has recently received FDA approval for clinical use for the treatment of adult and pediatric patients with relapsed or refractory MLLr acute leukemia. Notably, menin also interacts with the AP-1 transcription factor JUND through a conserved sequence identical to that required for MLL-FP binding. Despite this structural similarity, the impact of menin-MLL inhibitors on JUND function has remained unexplored. Results: In this study, we investigated the influence of menin-MLL inhibitors on JUND activity. Quantitative mass spectrometry analysis of MLLr leukemia cells treated with menin-MLL inhibitors demonstrated that they also disrupt menin-JUND protein interactions. Furthermore, CRISPR-mediated inactivation of JUND or pharmacological inhibition using JNK inhibitors synergistically enhanced the anti-leukemic effects of menin-MLL inhibitors, leading to reduced cell proliferation, cell cycle arrest and apoptosis. RNA sequencing and chromatin binding assays revealed that menin-MLL inhibitor treatment increases JUND chromatin occupancy, leading to upregulation of target gene expression and potentially contributing to the development of resistance to menin-MLL inhibitors. Mouse models engrafted with JUND-deficient leukemia cells exhibited reduced tumor burden compared to control mice engrafted with wild type leukemic cells. Conclusion: These findings suggest that targeting JUND activity may significantly enhance the efficacy of menin-MLL inhibitors towards MLLr leukemia cells.
2026-07-28 | PXD068056 | Pride
Project description:Background: MLL-rearranged (MLLr) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) involve reciprocal oncogenic translocations of the KMT2A/KMT2B (MLL1/MLL2) gene on chromosome 11q23 with various translocation partner genes, which yields to chimeric MLL fusion proteins (MLL-FPs). Menin, the protein product of the MEN1 gene, is essential for the leukemogenic activity of MLL-FPs. Revumenib, a small-molecule inhibitor that selectively disrupts the menin-MLL interaction, has recently received FDA approval for clinical use for the treatment of adult and pediatric patients with relapsed or refractory MLLr acute leukemia. Notably, menin also interacts with the AP-1 transcription factor JUND through a conserved sequence identical to that required for MLL-FP binding. Despite this structural similarity, the impact of menin-MLL inhibitors on JUND function has remained unexplored. Results: In this study, we investigated the influence of menin-MLL inhibitors on JUND activity. Quantitative mass spectrometry analysis of MLLr leukemia cells treated with menin-MLL inhibitors demonstrated that they also disrupt menin-JUND protein interactions. Furthermore, CRISPR-mediated inactivation of JUND or pharmacological inhibition using JNK inhibitors synergistically enhanced the anti-leukemic effects of menin-MLL inhibitors, leading to reduced cell proliferation, cell cycle arrest and apoptosis. RNA sequencing and chromatin binding assays revealed that menin-MLL inhibitor treatment increases JUND chromatin occupancy, leading to upregulation of target gene expression and potentially contributing to the development of resistance to menin-MLL inhibitors. Mouse models engrafted with JUND-deficient leukemia cells exhibited reduced tumor burden compared to control mice engrafted with wild type leukemic cells. Conclusion: These findings suggest that targeting JUND activity may significantly enhance the efficacy of menin-MLL inhibitors towards MLLr leukemia cells.
2026-07-28 | PXD068061 | Pride
Project description:Background: MLL-rearranged (MLLr) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) involve reciprocal oncogenic translocations of the KMT2A/KMT2B (MLL1/MLL2) gene on chromosome 11q23 with various translocation partner genes, which yields to chimeric MLL fusion proteins (MLL-FPs). Menin, the protein product of the MEN1 gene, is essential for the leukemogenic activity of MLL-FPs. Revumenib, a small-molecule inhibitor that selectively disrupts the menin-MLL interaction, has recently received FDA approval for clinical use for the treatment of adult and pediatric patients with relapsed or refractory MLLr acute leukemia. Notably, menin also interacts with the AP-1 transcription factor JUND through a conserved sequence identical to that required for MLL-FP binding. Despite this structural similarity, the impact of menin-MLL inhibitors on JUND function has remained unexplored. Results: In this study, we investigated the influence of menin-MLL inhibitors on JUND activity. Quantitative mass spectrometry analysis of MLLr leukemia cells treated with menin-MLL inhibitors demonstrated that they also disrupt menin-JUND protein interactions. Furthermore, CRISPR-mediated inactivation of JUND or pharmacological inhibition using JNK inhibitors synergistically enhanced the anti-leukemic effects of menin-MLL inhibitors, leading to reduced cell proliferation, cell cycle arrest and apoptosis. RNA sequencing and chromatin binding assays revealed that menin-MLL inhibitor treatment increases JUND chromatin occupancy, leading to upregulation of target gene expression and potentially contributing to the development of resistance to menin-MLL inhibitors. Mouse models engrafted with JUND-deficient leukemia cells exhibited reduced tumor burden compared to control mice engrafted with wild type leukemic cells. Conclusion: These findings suggest that targeting JUND activity may significantly enhance the efficacy of menin-MLL inhibitors towards MLLr leukemia cells.
2026-07-28 | PXD068124 | Pride
Project description:Background: MLL-rearranged (MLLr) acute myeloid leukemia (AML) and acute lymphoid leukemia (ALL) involve reciprocal oncogenic translocations of the KMT2A/KMT2B (MLL1/MLL2) gene on chromosome 11q23 with various translocation partner genes, which yields to chimeric MLL fusion proteins (MLL-FPs). Menin, the protein product of the MEN1 gene, is essential for the leukemogenic activity of MLL-FPs. Revumenib, a small-molecule inhibitor that selectively disrupts the menin-MLL interaction, has recently received FDA approval for clinical use for the treatment of adult and pediatric patients with relapsed or refractory MLLr acute leukemia. Notably, menin also interacts with the AP-1 transcription factor JUND through a conserved sequence identical to that required for MLL-FP binding. Despite this structural similarity, the impact of menin-MLL inhibitors on JUND function has remained unexplored. Results: In this study, we investigated the influence of menin-MLL inhibitors on JUND activity. Quantitative mass spectrometry analysis of MLLr leukemia cells treated with menin-MLL inhibitors demonstrated that they also disrupt menin-JUND protein interactions. Furthermore, CRISPR-mediated inactivation of JUND or pharmacological inhibition using JNK inhibitors synergistically enhanced the anti-leukemic effects of menin-MLL inhibitors, leading to reduced cell proliferation, cell cycle arrest and apoptosis. RNA sequencing and chromatin binding assays revealed that menin-MLL inhibitor treatment increases JUND chromatin occupancy, leading to upregulation of target gene expression and potentially contributing to the development of resistance to menin-MLL inhibitors. Mouse models engrafted with JUND-deficient leukemia cells exhibited reduced tumor burden compared to control mice engrafted with wild type leukemic cells. Conclusion: These findings suggest that targeting JUND activity may significantly enhance the efficacy of menin-MLL inhibitors towards MLLr leukemia cells.
2026-07-28 | PXD067825 | Pride
Project description:TRAP performed in GFP-RPL10A Min6 cells transfected with siRNA targeting Pdx1 or a non-targeting (NT) control. IP RNA was isolated by TRAP protocol and input lysate was used to isolate Total RNA. RNA-seq was performed on both IP and Total RNA.
2019-08-16 | GSE115219 | GEO
Project description:The goal of this experiment is to determine the effect of ATRX depletion on telomeric chromatin compaction. We adapted the ATAC-seq to quantify telomere chromatin accessibility. By scoring the ratio of sequence reads that contained 3 - 12 tandem telomeric repeats over the total number of reads in wild-type and ATRX deplted cells, our analysis revealed that CRISPR/Cas9-mediated ATRX depletion induces a progressive telomere de-compaction.
2019-08-26 | GSE130640 | GEO
Project description:To investigate the effects of the differences seen in the JUND binding patterns between LEW, WKY and WKY.LCrgn2 bone marrow derived macrophages (BMDMs), we have 1) analysed gene expression changes over a time course (4 time points: 0,2,4 and 8 hrs) of stimulation with lipopolysaccharide (LPS) using whole transcript expression microarrays, 2) knocked down JunD in WKY BMDMs and analysed gene expression by microarrays.
2013-04-01 | E-MEXP-3469 | biostudies-arrayexpress
Project description:We have generated JunD ChIPseq datasets of the human uterine smooth muscle (myometrium) tissue. ChIP-seq experiments were conducted to evaluate changes in the regions bound by JUND that occur as the smooth muscle cells transition from pregnancy to labour using human myometrium tissue.
2025-03-18 | GSE240816 | GEO