A5000627376- Ferroptosis and cancer prognosis
- RNA modifications and cancer
- Cancer, Lipids, and Metabolism
- MicroRNA in disease regulation
- Epigenetics and DNA Methylation
- Cancer-related molecular mechanisms research
- Gut microbiota and health
- Circular RNAs in diseases
- RNA Research and Splicing
- Reproductive System and Pregnancy
- Cancer-related gene regulation
- Genetic Neurodegenerative Diseases
- FOXO transcription factor regulation
- Neuroblastoma Research and Treatments
- Polyamine Metabolism and Applications
- Protein Kinase Regulation and GTPase Signaling
- TGF-β signaling in diseases
- NF-κB Signaling Pathways
- Wnt/β-catenin signaling in development and cancer
- PI3K/AKT/mTOR signaling in cancer
- Ubiquitin and proteasome pathways
- Colorectal Cancer Screening and Detection
- Neuroinflammation and Neurodegeneration Mechanisms
- Neonatal and fetal brain pathology
- Clusterin in disease pathology
Shandong University
2018-2025
Cancer Genetics (United States)
2016-2023
Columbia University
2016-2023
Taian City Central Hospital
2018-2023
Herbert Irving Comprehensive Cancer Center
2019
Jinan Central Hospital
2018
University of Science and Technology of China
2015
Significance Although it is commonly accepted that p53-mediated cell-cycle arrest, apoptosis, and senescence all serve as major mechanisms of tumor suppression, accumulating evidence indicates other activities p53, such ferroptosis, are also critical for suppression. However, the molecular by which ferroptosis operates not completely understood. In this study, we discovered p53 can execute ferroptotic cell-death responses directly activating its target gene SAT1 , coded spermidine/spermine N...
Abstract Here, we identify iPLA2β as a critical regulator for p53-driven ferroptosis upon reactive oxygen species (ROS)-induced stress. The calcium-independent phospholipase is known to cleave acyl tails from the glycerol backbone of lipids and release oxidized fatty acids phospholipids. We found that iPLA2β-mediated detoxification peroxidized sufficient suppress ROS-induced stress, even in GPX4-null cells. Moreover, overexpressed human cancers; inhibition endogenous sensitizes tumor cells...
Abstract It is well established that ferroptosis primarily induced by peroxidation of long-chain poly-unsaturated fatty acid (PUFA) through nonenzymatic oxidation free radicals or enzymatic stimulation lipoxygenase. Although there emerging evidence saturated (SFA) might be implicated in ferroptosis, it remains unclear whether and how SFA participates the process ferroptosis. Using endogenous metabolites genome-wide CRISPR screening, we have identified FAR1 as a critical factor for...
Abstract Emerging evidence reveals that amino acid metabolism plays an important role in ferroptotic cell death. The conversion of methionine to cysteine is well known protect tumour cells from ferroptosis upon starvation through transamination. However, whether acids‐produced metabolites participate independent the pathway largely unknown. Here, authors show tryptophan serotonin (5‐HT) and 3‐hydroxyanthranilic (3‐HA) remarkably facilitate escape distinct cysteine‐mediated inhibition....
Although it is well established that Huntington's disease (HD) mainly caused by polyglutamine-expanded mutant huntingtin (mHTT), the molecular mechanism of mHTT-mediated actions not fully understood. Here, we showed expression N-terminal fragment containing expanded polyglutamine (HTTQ94) mHTT able to promote both ACSL4-dependent and ACSL4-independent ferroptosis. Surprisingly, inactivation ferroptosis fails show any effect on life span mice. Moreover, using RNAi-mediated screening,...
Abstract Ferroptosis suppressor protein 1 (FSP1, also known as AIMF2, AMID or PRG3) is a recently identified glutathione-independent ferroptosis 1–3 , but its underlying structural mechanism remains unknown. Here we report the crystal structures of Gallus gallus FSP1 in substrate-free and ubiquinone-bound forms. The reveal FAD-binding domain NAD(P)H-binding domain, both which are shared with AIF NADH oxidoreductases 4–9 characteristic carboxy-terminal well. We demonstrate that crucial for...
S-palmitoylation is a reversible and widespread post-translational modification, but its role in the regulation of ferroptosis has been poorly understood. Here, we elucidate that GPX4, an essential regulator ferroptosis, reversibly palmitoylated on cysteine 66. The acyltransferase ZDHHC20 palmitoylates GPX4 increases protein stability. depletion or inhibition palmitoylation by 2-BP sensitizes cancer cells to ferroptosis. Moreover, identify APT2 as depalmitoylase GPX4. Genetic silencing...
Ferroptosis is a newly identified programmed cell death induced by iron-driven lipid peroxidation and implicated as potential approach for tumor treatment. However, emerging evidence indicates that hepatocellular carcinoma (HCC) cells are generally resistant to ferroptosis the underlying molecular mechanism poorly understood. Here, our study confirms S100 calcium binding protein P (S100P), which significantly up-regulated in ferroptosis-resistant HCC cells, efficiently inhibits ferroptosis....
Abstract Recent findings have shown that fatty acid metabolism is profoundly involved in ferroptosis. However, the role of cholesterol this process remains incompletely understood. In work, we show modulating levels changes vulnerability cells to Cholesterol alters metabolic flux mevalonate pathway by promoting Squalene Epoxidase (SQLE) degradation, a rate limiting step biosynthesis, thereby increasing both CoQ10 and squalene levels. Importantly, whereas inactivation Farnesyl-Diphosphate...
Redox‐based diagnostic and therapeutic applications have long suffered from a shortage of suitable drugs probes high specificity. In the context anti‐ferroptosis research for neurological diseases, inaccessibility blood‐brain barrier permeable (BBB) small molecular ferroptosis inhibitor, lack specific seriously impeded deeper understanding mechanism development clinically applicable drugs. We here report novel 1,3,4‑thiadiazole‐functionalized drug‐like ferrostatin analogue entitled...
Lipid metabolism is important for cellular energy homeostasis. Excessive lipid accumulation associated with various human diseases such as obesity, cardiovascular disease or even cancer. It has been recognized that miR-181a an modulator in regulating T lymphocyte differentiation, vascular development and cerebellar neurodegeneration. Here we reports a novel function of the regulation metabolism. MiR-181a able to target isocitrate dehydrogenase 1 (IDH1), metabolic enzyme TCA cycle. Via...
Embryo implantation is a crucial step in mammalian reproduction. However, little known regarding the physiological roles of microRNAs regulation embryo implantation. Here we show that minimum uterine expression miR-181 essential for onset Both transient and prolonged transgenic led to impaired implantation, which can be rescued by exogenous administration leukemia inhibitory factor (LIF). Mechanistically, able directly target LIF downregulate expression, thereby inhibiting We also regulated...
Abstract The uterine epithelium undergoes a dramatic spatiotemporal transformation to enter receptive state, involving complex interaction between ovarian hormones and signals from stromal epithelial cells. Redox homeostasis is critical for cellular physiological steady state; emerging evidence reveals that excessive lipid peroxides derail redox homeostasis, causing various diseases. However, the role of in early pregnancy remains largely unknown. It found deletion Glutathione peroxidase 4...
The G protein–coupled bile acid receptor (GPBAR) is the membrane for acids and a driving force of liver–bile acid–microbiota–organ axis to regulate metabolism other pathophysiological processes. Although GPBAR an important therapeutic target spectrum metabolic neurodegenerative diseases, its activation has also been found be linked carcinogenesis, leading potential side effects. Here, via functional screening, we that two specific agonists, R399 INT-777, demonstrated strikingly different...
Redox‐based diagnostic and therapeutic applications have long suffered from a shortage of suitable drugs probes high specificity. In the context anti‐ferroptosis research for neurological diseases, inaccessibility blood‐brain barrier permeable (BBB) small molecular ferroptosis inhibitor, lack specific seriously impeded deeper understanding mechanism development clinically applicable drugs. We here report novel 1,3,4‑thiadiazole‐functionalized drug‐like ferrostatin analogue entitled...
Abstract Ferroptosis is a newly identified cell death triggered by iron‐induced lipid peroxidation. Numerous studies reveal that ferroptosis participates in multiple types of tissue injury including ischaemia–reperfusion (I/R) and doxorubicin (Dox)‐induced damage. Targeting promising approach for disease treatment as the blockade efficiently alleviates symptoms. However, no known inhibitors have been used clinical treatment. Although certain compounds act vitro, whether these drugs cure...
MicroRNA-146a (miR-146a) is reportedly implicated in the pathogenesis of ischemia–reperfusion (I/R) injury; however, its role cerebral I/R injury unclear and requires further investigation. In this study, was established mice via middle artery occlusion, expression miR-146a detected brain tissue quantitative real-time PCR. We found that upregulated. Furthermore, endogenous antagonized by specific inhibitor. The results indicated inhibition deteriorated I/R-induced neurobehavioral impairment,...