AGPAT4

更新于：2025-05-07

基本信息

别名

1-acyl-sn-glycerol-3-phosphate acyltransferase delta、1-acylglycerol-3-phosphate O-acyltransferase 4、1-AGP acyltransferase 4

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简介

Converts 1-acyl-sn-glycerol-3-phosphate (lysophosphatidic acid or LPA) into 1,2-diacyl-sn-glycerol-3-phosphate (phosphatidic acid or PA) by incorporating an acyl moiety at the sn-2 position of the glycerol backbone (By similarity). Exhibits high acyl-CoA specificity for polyunsaturated fatty acyl-CoA, especially docosahexaenoyl-CoA (22:6-CoA, DHA-CoA) (By similarity).

关联

100 项与 AGPAT4 相关的临床结果

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100 项与 AGPAT4 相关的转化医学

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0 项与 AGPAT4 相关的专利（医药）

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项与 AGPAT4 相关的文献（医药）

2025-03-01·Cancer Medicine

Multi‐Omic Analysis Reveals a Lipid Metabolism Gene Signature and Predicts Prognosis and Chemotherapy Response in Thyroid Carcinoma

Article

作者: Liao, Pu ; Mo, Linlong ; Ji, Xinyao ; Yan, Guiling ; Chen, Shu ; Chen, Yanchen ; Tu, Yuqin ; Niu, Changchun ; Xie, Jingling

ABSTRACTObjectiveLipid metabolic reprogramming is closely intertwined with the development and progression of thyroid carcinoma (TC); however, its specific mechanism remains elusive. This study aimed to investigate the association between lipid metabolism and TC progression.MethodsWe employed liquid chromatography‐mass spectrometry (LC/MS) for an untargeted metabolomics analysis, comparing 12 TC patients and 12 healthy controls (HC). Additionally, we conducted the screening of differentially expressed genes (DEGs) and identified differentially expressed lipid metabolism genes (LMGs). Multi‐omic findings related to lipid metabolism were integrated to establish a prognostic risk model. The resulting risk score stratified TC patients into high‐ and low‐risk groups. Overall survival (O.S.) was assessed using Kaplan–Meier (K–M) analysis. The immune landscape was evaluated using the CIBERSORT algorithm, and chemotherapeutic response was predicted utilizing the “pRRophetic” R package.ResultsOur metabolomic analysis revealed heightened lipid metabolic activity in TC, corroborated by similar findings in transcriptomic analysis. Multi‐omic analysis identified key LMGs (FABP4, PPARGC1A, AGPAT4, ALDH1A1, TGFA, and GPAT3) associated with fatty acids and glycerophospholipids metabolism. A novel risk model, incorporating these LMGs, confirmed significantly worse O.S. (p = 0.0045) in the high‐risk group based on TCGA_THCA. Furthermore, high‐risk TC patients exhibited lower immune cell infiltration, and predictive outcomes indicated the efficacy of potential therapeutic drugs across risk groups.ConclusionThis multi‐omic analysis underscores the potential utility of the lipid metabolism risk model in guiding clinical treatment and improving outcomes for TC patients.

2024-10-01·Human Genetics

Unraveling the significance of AGPAT4 for the pathogenesis of endometriosis via a multi-omics approach

Article

作者: Shen, Licong ; Chen, Jun ; Yang, Yongwen ; Wu, Tingting

AbstractEndometriosis is characterized by the ectopic proliferation of endometrial cells, posing considerable diagnostic and therapeutic challenges. Our study investigates AGPAT4’s involvement in endometriosis pathogenesis, aiming to unveil new therapeutic targets. Our investigation by analyzing eQTL data from GWAS for preliminary screening. Subsequently, within the GEO dataset, we utilized four machine learning algorithms to precisely identify risk-associated genes. Gene validity was confirmed through five Mendelian Randomization methods. AGPAT4 expression was measured by Single-Cell Analysis, ELISA and immunohistochemistry. We investigated AGPAT4’s effect on endometrial stromal cells using RNA interference, assessing cell proliferation, invasion, and migration with CCK8, wound-healing, and transwell assays. Protein expression was analyzed by western blot, and AGPAT4 interactions were explored using AutoDock. Our investigation identified 11 genes associated with endometriosis risk, with AGPAT4 and COMT emerging as pivotal biomarkers through machine learning analysis. AGPAT4 exhibited significant upregulation in both ectopic tissues and serum samples from patients with endometriosis. Reduced expression of AGPAT4 was observed to detrimentally impact the proliferation, invasion, and migration capabilities of endometrial stromal cells, concomitant with diminished expression of key signaling molecules such as Wnt3a, β-Catenin, MMP-9, and SNAI2. Molecular docking analyses further underscored a substantive interaction between AGPAT4 and Wnt3a.Our study highlights AGPAT4’s key role in endometriosis, influencing endometrial stromal cell behavior, and identifies AGPAT4 pathways as promising therapeutic targets for this condition.

2024-01-01·FASEB BioAdvances

Oleic acid stimulation of amino acid uptake in primary human trophoblast cells is mediated by phosphatidic acid and mTOR signaling

Article

作者: Chassen, Stephanie ; Madi, Lana ; Jansson, Thomas ; Silva, Elena ; Powell, Theresa L. ; Kramer, Anita ; Pantham, Priyadarshini ; Ferchaud‐Roucher, Véronique

AbstractNormal fetal development is critically dependent on optimal nutrient supply by the placenta, and placental amino acid transport has been demonstrated to be positively associated with fetal growth. Mechanistic target of rapamycin (mTOR) is a positive regulator of placental amino acid transporters, such as System A. Oleic acid (OA) has been previously shown to have a stimulatory role on placental mTOR signaling and System A amino acid uptake in primary human trophoblast (PHT) cells. We investigated the mechanistic link between OA and System A activity in PHT. We found that inhibition of mTOR complex 1 or 2, using small interfering RNA to knock down raptor or rictor, prevented OA‐stimulated System A amino acid transport indicating the interaction of OA with mTOR. Phosphatidic acid (PA) is a key intermediary for phospholipid biosynthesis and a known regulator of the mTOR pathway; however, phospholipid biosynthetic pathways have not been extensively studied in placenta. We identified placental isoforms of acyl transferase enzymes involved in de novo phospholipid synthesis. Silencing of 1‐acylglycerol‐3‐phosphate‐O‐acyltransferase‐4, an enzyme in this pathway, prevented OA mediated stimulation of mTOR and System A amino acid transport. These data indicate that OA stimulates mTOR and amino acid transport in PHT cells mediated through de novo synthesis of PA. We speculate that fatty acids in the maternal circulation, such as OA, regulate placental functions critical for fetal growth by interaction with mTOR and that late pregnancy hyperlipidemia may be critical for increasing nutrient transfer to the fetus.

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