LncRNA NDRG1-OT1 downstream gene microarray
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE72881 | GEO | 2017/12/31
SECONDARY ACCESSION(S): PRJNA295258
REPOSITORIES: GEO
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Project description:Coronary artery disease (CAD) remains the leading cause of mortality worldwide. Macrophages play a crucial role in recruiting immune cells and regulating the inflammatory milieu through the release of a diverse array of cytokines, chemokines, and other immune mediators in CAD. Long noncoding RNAs (lncRNAs) interact with DNA, RNA, miRNA, and proteins, making them attractive therapeutic targets for regulating gene expression. Methods and Results: Gene-expression meta-analysis and weighted gene co-expression network analysis (WGCNA) of human CAD datasets identified 26 lncRNA-mRNA co-expression modules. Network prioritization of top co-expression modules identified SPANXA2-OT1 as a potential key candidate. Conservation analysis revealed that SPANXA2-OT1 is human specific and conserved only in primates. We validated the candidate coding-noncoding RNA regulatory triad in human primary macrophages derived from healthy human peripheral blood mononuclear cells (PBMCs). IL-1β induced the expression of SPANXA2-OT1. RNA in situ hybridization localized SPANXA2-OT1 mRNA in cytoplasm of macrophages. Loss-of-function experiments using antisense oligonucleotide (ASO) against SPANXA2-OT1 demonstrated decreased monocyte/macrophage chemotaxis signature after SPANXA2-OT1 silencing, as demonstrated by unbiased global proteomics and RNAseq data. Luciferase assay established that SPANXA2-OT1 binds to miR-338 through its miRNA response elements. Gain-of-function (miR-338 mimic) and loss-of-function (SPANXA2-OT1 ASO) experiments revealed that SPANXA2-OT1-miR-338 axis regulates the expression of monocyte chemotactic genes (e.g., IL-8) that may contribute to the pathophysiology of CAD. CRISPR/Cas9 mediated deletion of the SPANXA2-OT1 functional domain (exon 3, which harbors the miR-338 binding site) in human primary macrophages resulted in decreased IL-8 expression, alteration of the chemokine profile, and decreased macrophage chemotaxis. Conclusion: Our results indicate that the lncRNA SPANXA2-OT1 regulates chemokine signatures and macrophage chemotaxis. One such mechanism involves SPANXA2-OT1 binding to miR-338, making it unavailable to regulate IL-8 expression. Our findings may provide a molecular basis for the future identification of novel biomarkers and therapeutic targets for CAD.
2025-09-10 | PXD059474 | Pride
Project description:Coronary artery disease (CAD) remains the leading global cause of death, with macrophages playing a central role in driving inflammation through cytokines, chemokines, and other mediators. Using gene expression meta-analysis and weighted gene co-expression network analysis (WGCNA) of human CAD datasets, we identified 26 lncRNA–mRNA modules and prioritized SPANXA2-OT1 as a key inflammation regulator. Conservation analysis revealed SPANXA2-OT1 to be primate-specific, necessitating human macrophage models derived from PBMCs. IL-1β stimulation induced cytoplasmic SPANXA2-OT1, and antisense oligonucleotide-mediated silencing reduced chemotaxis signatures, validated by RNA-seq and proteomics. Mechanistically, SPANXA2-OT1 directly bound miR-338, as shown by luciferase assays, thereby regulating IL-8 and related chemokines critical for monocyte recruitment. CRISPR/Cas9 deletion of exon 3 further confirmed reduced IL-8 expression and impaired macrophage chemotaxis. Collectively, these findings establish SPANXA2-OT1 as a human-specific regulator of macrophage-driven inflammation in CAD and highlight its promise as a translational biomarker and therapeutic target.
2025-09-09 | GSE307322 | GEO
Project description:N-myc downstream-regulated gene 1 (*NDRG1*) is induced by cellular stress such as hypoxia and DNA damage, and in humans, germ line mutations cause Charcot-Marie-Tooth disease. However, the roles of NDRG1 in the cell are not fully understood. Previously, NDRG1 was shown to mediate doxorubicin resistance under hypoxia, suggesting a role for NDRG1 in cell survival under these conditions. We found decreased apoptosis in doxorubicin-treated cells expressing NDRG1 shRNAs under normoxia, demonstrating a requirement for NDRG1 in apoptosis in breast epithelial cells under normal oxygen pressure. We further compared expression profiles in human breast epithelial cells ectopically over-expressing NDRG1 with cells expressing NDRG1 shRNAs in order to identify biological pathways where NDRG1 is involved. The results suggest that NDRG1 may have roles connected to vesicle transport. The previously reported roles of NDRG1 in apoptosis, myelin sheet maintenance, enhanced exocytosis in mast cells and in cellular responses to hypoxia, heavy metals, and androgen may all converge by NDRG1 having a role linked to vesicle transport.
2011-11-04 | GSE33437 | GEO
Project description:N-myc downstream-regulated gene 1 (*NDRG1*) is induced by cellular stress such as hypoxia and DNA damage, and in humans, germ line mutations cause Charcot-Marie-Tooth disease. However, the roles of NDRG1 in the cell are not fully understood. Previously, NDRG1 was shown to mediate doxorubicin resistance under hypoxia, suggesting a role for NDRG1 in cell survival under these conditions. We found decreased apoptosis in doxorubicin-treated cells expressing NDRG1 shRNAs under normoxia, demonstrating a requirement for NDRG1 in apoptosis in breast epithelial cells under normal oxygen pressure. We further compared expression profiles in human breast epithelial cells ectopically over-expressing NDRG1 with cells expressing NDRG1 shRNAs in order to identify biological pathways where NDRG1 is involved. The results suggest that NDRG1 may have roles connected to vesicle transport. The previously reported roles of NDRG1 in apoptosis, myelin sheet maintenance, enhanced exocytosis in mast cells and in cellular responses to hypoxia, heavy metals, and androgen may all converge by NDRG1 having a role linked to vesicle transport. SUM102 and ME16C2 stably transduced with siRNA against NDRG1 compared with empty vector control ZR-75-1 stably transduced with NDRG1 overexpression construct compared with empty vector control Two condition design
2011-11-04 | E-GEOD-33437 | biostudies-arrayexpress
Project description:Long non-coding RNAs (lncRNAs) have been regarded to participate in multiple genetic pathways in cancer. Also, mitochondria-associated lncRNAs have been discovered to module mitochondrial function and metabolism. Previously, our lab identified oxygen responsive lncRNAs in breast cancer MCF-7 cells under normoxic, hypoxic and re-oxygenated conditions by using next generation sequencing technology. Among them, a novel mitochondrial lncRNA Mitochondrial Oxygen Responsive Transcript 1 (MTORT1) was chosen for further investigation. Therefore, the purpose of this study was to investigate the characterizations, function roles, and mechanisms of MTORT1 in breast cancer cells.
2021-06-23 | GSE157060 | GEO
Project description:N-myc downstream regulated gene 1 (NDRG1) is a member of the NDRG family of intracellular proteins, and plays a central role in a wide range of biological processes including stress response, differentiation, and maintenance of the myelin sheath. The overexpression of NDRG1 is an indicator of poor prognosis in various pathological conditions. Here, we found that NDRG1 is an independent prognostic marker of poor outcome in breast cancer (BC). NDRG1 expression is regulated by a variety of molecular mechanisms, including transcriptional and post-translational control. In the present study, CRISPR-based inactivation of NDRG1 allowed us to demonstrate that this protein is required for breast cancer cell invasion, without affecting viability. We observed that different acute stress conditions converge on protein kinase C (PKC) activation driving enhanced NDRG1 expression through a signaling pathway that involves ROCK/AMPK/Akt kinases. This newly discovered mechanism was specific for NDRG1 as the expression of other NDRG members was not affected. Together, our results suggest that pathophysiological PKC-mediated activation of NDRG1 may be a response mechanism to metabolic stress and anticancer agents.
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Project description:WT and KO OT1 T cells were isolated from vaccinia-OVA infected ears 21 days post infection
2023-08-08 | GSE223727 | GEO
Project description:SKBR3 cells expressing NDRG1 shRNA1 or vector control were harvested by trypsinization and total RNA was extracted. Silencing NDRG1 reduces cell proliferation rates, causing lipid metabolism dysfunction including increased fatty acid incorporation into neutral lipids and lipid droplets. global changes in transcriptome due to NDRG1 silencing were observed
2018-06-21 | GSE112841 | GEO
Project description:Time course of OT1 T cell activation with SIINFEKL peptide.
2020-02-25 | PXD016443 | Pride