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Critical Role of MALAT1 in Gram-negative Bacteria-induced Coagulation via regulating GSDMD-dependent TF activity

ABSTRACT: The study determines the transcriptosome of leukocytes from septic patients upon admission who were infected with gram-negative bacteria and not diagnosed with overt disseminated intravascular coagulation (DIC).Higher levels of MALAT1 are associated with the onset of DIC 48 hours after the admission.

ORGANISM(S): Homo sapiens

PROVIDER: GSE267399 | GEO | 2025/12/31

REPOSITORIES: GEO

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Neutrophils restrain sepsis associated coagulopathy via extracellular vesicles carrying superoxide dismutase 2 in a murine model of lipopolysaccharide induced sepsis

Project description:Disseminated intravascular coagulation (DIC) is a deadly complication of sepsis lacking effective managements. Although excessive inflammatory responses are emerging as key triggers of coagulopathy in sepsis, the interplays between immune system and coagulation are not fully understood. In a murine model of sepsis induced by intraperitoneal lipopolysaccharide (LPS), we found neutrophils in circulation mitigate the occurrence of DIC, thereby preventing the subsequent septic death. We found circulating neutrophils constantly release extracellular vesicles (EVs) containing mitochondria, which carry substantial amount of Superoxide Dismutase 2 (Sod2) upon LPS exposure. The extracellular Sod2 is necessary to bring about neutrophils’ antithrombotic function by eliminating endothelial reactive oxygen species (ROS) accumulation and alleviating endothelial dysfunction. Intervening endothelial ROS accumulation by antioxidants significantly ameliorates DIC with correspondingly improved survival in sepsis. These findings revealed a novel interaction between neutrophils and vascular endothelium which critically regulates coagulation in sepsis and had potential implications for the management of septic DIC.

2022-07-26 | GSE206825 | GEO

Critical Role of MALAT1 in Gram-negative Bacteria-induced Coagulation via regulating GSDMD-dependent TF activity

Project description:Critical Role of MALAT1 in Gram-negative Bacteria-induced Coagulation via regulating GSDMD-dependent TF activity

| PRJNA1111413 | ENA

Differential Gene expression in the mouse mammary tumors of PyMT-Malat1 wild-type (WT), PyMT-Malat1 knockout (KO) and PyMT-Malat1 knockout with Malat1 transgene expression (TG)

Project description:Previously, lncRNA Malat1 knockout mice were generated by insertional inactivation. By crossing this line to MMTV-PyMT mammary tumor mouse model, we produced PyMT;Malat1 wild-type (WT) and PyMT;Malat1 knockout (KO). Furthermore, we generated Malat1 transgenic mice by targeting ROSA26 locus and bred them to PyMT;Malat1 knockout mice to produce Malat1-rescued PyMT;Malat1 knockout;Malat1 transgenic animals (TG). Using mammary tumors from the three groups of animals, we performed RNA-Seq analysis to identify differentially up-regulated genes in KO tumors to find novel target genes of YAP-TEAD pathway.

2018-09-18 | GSE110239 | GEO

Effects of the long noncoding RNA Malat1 on gene expression [Mouse430_2]

Project description:Malat1 is an abundant long noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous in vitro studies have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine- and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-KO (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long noncoding RNA, Neat1, which is an architectural component of nuclear bodies known as paraspeckles, were downregulated in a particular set of tissues and cells lacking Malat1. To address if the the absence of Malat1 affects the expression of other genes, including other long noncoding RNA, microarrays were used to study the impact of knocking-out Malat1 on global gene expression in mouse embryonic fibroblasts (MEFs). MEFs were prepared from E13.5 mouse embryos from wildtype and Malat1 knock-out mice. RNA harvested from these cells were hybridized to Affymetirx mouse gene expression array.

2012-06-24 | E-GEOD-37705 | biostudies-arrayexpress

lncRNA MALAT1 interactome - Quantitative proteomics reveals that long non-coding RNA MALAT1 interacts with DBC1 to regulate p53 acetylation

Project description:Metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) is a long non-coding RNA (lncRNA) that was first discovered as a prognostic marker for lung cancer metastasis. MALAT1 has been implicated in the tumorigenesis of numerous tumor types. To further delineate the underlying molecular mechanism, we established a high-throughput strategy to characterize the interacting proteins of MALAT1 by combining RNA pull down, quantitative proteomics, bioinformatics analysis, and experimental validation.

2018-10-26 | PXD005154 | Pride

Effects of the long noncoding RNA Malat1 on gene expression [MoEx-1_0-st]

Project description:Malat1 is an abundant long noncoding RNA that localizes to nuclear bodies known as nuclear speckles, which contain a distinct set of pre-mRNA processing factors. Previous in vitro studies have demonstrated that Malat1 interacts with pre-mRNA splicing factors, including the serine- and arginine-rich (SR) family of proteins, and regulates a variety of biological processes, including cancer cell migration, synapse formation, cell cycle progression, and responses to serum stimulation. To address the physiological function of Malat1 in a living organism, we generated Malat1-KO (KO) mice using homologous recombination. Unexpectedly, the Malat1-KO mice were viable and fertile, showing no apparent phenotypes. Nuclear speckle markers were also correctly localized in cells that lacked Malat1. However, the cellular levels of another long noncoding RNA, Neat1, which is an architectural component of nuclear bodies known as paraspeckles, were downregulated in a particular set of tissues and cells lacking Malat1. To address if the absence of Malat1 affects the expression of other genes, including other long noncoding RNA, microarrays were used to study the impact of knocking-out Malat1 on global gene expression in hippocampal neurons. Hippocampi were dissected from two sets of wildtype and Malat1 knock-out mice and RNA from these neurons were hybridized to Affymetix mouse exon array. Individual animals from each pairs of wildtype and knock-out are littermates.

2012-06-24 | E-GEOD-37706 | biostudies-arrayexpress

Malat1 regulates intestinal epithelial cell function

Project description:The long-non-coding RNA Malat1 is abundantly expressed in all subsets of the intestinal epithelial cells (IEC). Here, we compared the transcriptome of the small intestinal and colonic epithelium of wildtype and Malat1-/- mice under steady state. We found that Malat1 is involved in IEC homeostasis, intestinal microbial balance, and regulates programs involved in intestinal cancer.

2023-04-28 | GSE208232 | GEO

Effects of the long noncoding RNA Malat1 on gene expression

Project description:This SuperSeries is composed of the following subset Series: GSE37705: Effects of the long noncoding RNA Malat1 on gene expression [Mouse430_2] GSE37706: Effects of the long noncoding RNA Malat1 on gene expression [MoEx-1_0-st] Refer to individual Series

2012-06-24 | E-GEOD-37707 | biostudies-arrayexpress

Differentiation of Mammary Tumors and Reduction in Metastasis Upon Malat1 LncRNA Loss

Project description:Genome-wide analyses have identified thousands of long non-coding RNAs (lncRNAs). Malat1 (Metastasis Associated Lung Adenocarcinoma Transcript 1) is among the most abundant lncRNAs whose expression is altered in numerous cancers. Here we report that genomic loss, as well as systemic knockdown of Malat1 using antisense oligonucleotides, in the MMTV-PyMT mouse mammary carcinoma model results in slower tumor growth accompanied by differentiation into highly cystic tumors and a significant reduction in lung metastasis. Further, Malat1 loss results in a reduction of branching morphogenesis in MMTV-PyMT and Her2/neu amplified tumor organoids consistent with the in vivo reduction in lung metastasis. At the molecular level, Malat1 knockdown results in alterations in gene expression and changes in splicing patterns of genes involved in differentiation and pro-tumorigenic signaling pathways. Together, these data indicate that the lncRNA Malat1 regulates critical processes in mammary cancer pathogenesis and represents a promising therapeutic target for inhibiting breast cancer metastasis. Transcriptome profiles of tumors and organoids after Malat1 knockdown using antisense olgonucleotides (ASOs).

2016-01-12 | E-GEOD-67647 | biostudies-arrayexpress

Early predictive factors of mortality in onco-hematology patients admitted to the Intensive Care Unit for septic shock: A proteomic approach.

Project description:The number of organ failures at intensive care unit (ICU) admission is the main prognostic factor in septic shock. The aim was to assess classical clinico-biological parameters evaluating organ dysfunctions at ICU admission, combined with proteomics analysis, on day-30 mortality in critically ill onco-hematology patients admitted to the ICU for septic shock.

2018-08-22 | PXD004001 | Pride

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