A5032802010- Nuclear Receptors and Signaling
- Macrophage Migration Inhibitory Factor
- Autophagy in Disease and Therapy
- Epigenetics and DNA Methylation
- MicroRNA in disease regulation
- RNA modifications and cancer
- Circular RNAs in diseases
- Inflammasome and immune disorders
- Adenosine and Purinergic Signaling
- Cancer-related Molecular Pathways
- Fatty Acid Research and Health
- RNA Research and Splicing
- Immune cells in cancer
- Apelin-related biomedical research
- Extracellular vesicles in disease
- Cell death mechanisms and regulation
- Wnt/β-catenin signaling in development and cancer
- Organic Chemistry Cycloaddition Reactions
- Retinoids in leukemia and cellular processes
- Synthesis of Tetrazole Derivatives
- Signaling Pathways in Disease
- RNA regulation and disease
- GDF15 and Related Biomarkers
- Cancer-related molecular mechanisms research
- Whipple's Disease and Interleukins
Xiamen University
2012-2024
National University of Singapore
2008
Iron has been shown to trigger oxidative stress by elevating reactive oxygen species (ROS) and participate in different modes of cell death, such as ferroptosis, apoptosis necroptosis. However, whether iron-elevated ROS is also linked pyroptosis not reported. Here, we demonstrate that iron-activated can induce via a Tom20-Bax-caspase-GSDME pathway. In melanoma cells, iron enhanced signaling initiated CCCP, causing the oxidation oligomerization mitochondrial outer membrane protein Tom20. Bax...
Abstract Pyroptosis is a form of regulated cell death mediated by gasdermin family members, among which the function GSDMC has not been clearly described. Herein, we demonstrate that metabolite α-ketoglutarate (α-KG) induces pyroptosis through caspase-8-mediated cleavage GSDMC. Treatment with DM-αKG, cell-permeable derivative α-KG, elevates ROS levels, leads to oxidation plasma membrane-localized receptor DR6. Oxidation DR6 triggers its endocytosis, and then recruits both pro-caspase-8...
Extracellular vesicles play crucial roles in intercellular communication the tumor microenvironment. Here we demonstrate that hepatic fibrosis, TGF-β stimulates palmitoylation of hexokinase 1 (HK1) stellate cells (HSCs), which facilitates secretion HK1 via large extracellular a TSG101-dependent manner. The vesicle is hijacked by hepatocellular carcinoma (HCC) cells, leading to accelerated glycolysis and HCC progression. In HSCs, nuclear receptor Nur77 transcriptionally activates expression...
Abstract Pyroptosis is a type of regulated cell death executed by gasdermin family members. However, how gasdermin-mediated pyroptosis negatively remains unclear. Here, we demonstrate that mannose, hexose, inhibits GSDME-mediated activating AMP-activated protein kinase (AMPK). Mechanistically, mannose metabolism in the hexosamine biosynthetic pathway increases levels metabolite N -acetylglucosamine-6-phosphate (GlcNAc-6P), which binds AMPK to facilitate phosphorylation LKB1. Activated then...
Abstract Gluconeogenesis, an essential metabolic process for hepatocytes, is downregulated in hepatocellular carcinoma (HCC). Here we show that the nuclear receptor Nur77 a tumour suppressor HCC regulates gluconeogenesis. Low expression clinical samples correlates with poor prognosis, and deficiency mice promotes development. interacts phosphoenolpyruvate carboxykinase (PEPCK1), rate-limiting enzyme gluconeogenesis, to increase gluconeogenesis suppress glycolysis, resulting ATP depletion...
Significance It is still a great challenge to identify novel therapeutic strategies for breast cancer, especially those with treatment resistance. was demonstrated here that nuclear receptor Nur77 an effective drug target cancer and compound Csn-B clinically relevant by binding prevent peroxisome proliferator-activated receptor-γ (PPARγ) targeting steric hindrance, thereby inhibiting fatty acid uptake in cells mouse models. Clinical sample analysis further supported the opposing roles of...
The Hippo signaling pathway maintains organ size and tissue homeostasis via orchestration of cell proliferation apoptosis. How this triggers apoptosis remains largely unexplored. Here, we identify NR4A1 as a target the that mediates pro-apoptotic anti-tumor effects whereby YAP regulates transcription, phosphorylation, mitochondrial localization NR4A1. NR4A1, in turn, functions feedback inhibitor to promote its degradation, thereby inhibiting function during liver regeneration tumorigenesis....
Nur77 is a steroid orphan receptor that plays critical role in regulating proliferation, differentiation, and apoptosis, including acting as switch for Bcl-2 function. We previously reported the octaketide cytosporone B (Csn-B) natural agonist Nur77. In this study, we synthesized series of Csn-B analogues performed structure-activity analysis suggested criteria development unique pharmacophore to activate The components necessary binding included benzene ring, phenolic hydroxyl group, acyl...
Abstract Hepatocellular carcinoma (HCC) is one of the leading causes cancer-related mortality worldwide. Orphan nuclear receptor Nur77, which low expressed in HCC, functions as a tumor suppressor to suppress HCC. However, detailed mechanism still not well understood. Here, we demonstrate that Nur77 could inhibit HCC development via transcriptional activation lncRNA WAP four-disulfide core domain 21 pseudogene (WFDC21P). binds its response elements on WFDC21P promoter directly induce...
<h3>Aims</h3> Wnt signalling is involved in cellular homeostasis and development. Dysregulation of the pathway has been linked to colorectal cancer. The orphan nuclear receptor TR3 plays important roles proliferation apoptosis. In this study, we investigated how suppresses intestinal tumorigenesis by regulating signalling. <h3>Methods</h3> Intestinal polyps were quantified <i>Apc<sup>min/+</sup></i>, <i>Apc<sup>min/+</sup>/TR3<sup>−/−</sup></i> <i>Apc<sup>min/+</sup>/villin-TR3</i> mice....
Leptin, an anorexigenic hormone in the hypothalamus, suppresses food intake and increases energy expenditure. Failure to respond leptin will lead obesity. Here, we discovered that nuclear receptor Nur77 expression is lower hypothalamus of obese mice compared with normal mice. Injection results significant reduction body weight wild-type but not knockout (KO) littermates or specific knockdown hypothalamus. Hypothalamic only participates central control also expands leptin's reach liver...
In response to ionizing radiation (IR)-induced DNA double-strand breaks (DSB), cells elicit an evolutionarily conserved checkpoint that induces cell cycle arrest and either repair or apoptosis, thereby maintaining genomic stability. DNA-dependent protein kinase (DNA-PK) is a central enzyme involved in DSB for mammalian comprises DNA-PK catalytic subunit the Ku protein, which act as regulatory elements. also functions signaling molecule selectively regulate p53-dependent apoptosis IR. Herein,...
Abstract p62 is a receptor that facilitates selective autophagy by interacting simultaneously with cargoes and LC3 protein on the autophagosome to maintain cellular homeostasis. However, regulatory mechanism(s) behind this process its association breast cancer remain be elucidated. Here, we report Flightless-I (FliI), novel p62-interacting protein, promotes progression impeding autophagy. FliI was highly expressed in clinical samples, heterozygous deletion of retarded development mammary...
Cisplatin is a widely used antitumor agent that induces aggressive cancer cell death via triggering cellular proteins involved in apoptosis. Here, we demonstrate cisplatin effectively orphan nuclear receptor TR3 phosphorylation by activating Chk2 kinase activity and promoting cross talk between these two proteins, thereby contributing to the repression of intestinal tumorigenesis Mechanistic analysis has demonstrated Chk2-induced enables bind its response elements on promoters BRE RNF-7...