Identification of biomarkers and potential drug targets for esophageal cancer: a Mendelian randomization study

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: March 10, 2025

Language: Английский

From Classical to Alternative Pathways of 2-Arachidonoylglycerol Synthesis: AlterAGs at the Crossroad of Endocannabinoid and Lysophospholipid Signaling

Molecules, Journal Year: 2024, Volume and Issue: 29(15), P. 3694 - 3694

Published: Aug. 4, 2024

2-arachidonoylglycerol (2-AG) is the most abundant endocannabinoid (EC), acting as a full agonist at both CB1 and CB2 cannabinoid receptors. It synthesized on demand in postsynaptic membranes through sequential action of phosphoinositide-specific phospholipase Cβ1 (PLCβ1) diacylglycerol lipase α (DAGLα), contributing to retrograde signaling upon interaction with presynaptic CB1. However, 2-AG production might also involve various combinations PLC DAGL isoforms, well additional intracellular pathways implying other enzymes substrates. Three alternative synthesis rest extracellular cleavage 2-arachidonoyl-lysophospholipids by three different hydrolases: glycerophosphodiesterase 3 (GDE3), lipid phosphate phosphatases (LPPs), two members ecto-nucleotide pyrophosphatase/phosphodiesterases (ENPP6-7). We propose names AlterAG-1, -2, -3 for sharing an ectocellular localization, allowing them convert lysophospholipid mediators into 2-AG, thus inducing typical switches between G-protein-coupled receptors (GPCRs). This implies critical importance regioisomerism (LPLs) which object deep analysis within this review. The precise functional roles AlterAGs are still poorly understood will require gene invalidation approaches, knowing that its related lysophospholipids involved numerous aspects physiology pathology, including cancer, inflammation, immune defenses, obesity, bone development, neurodegeneration, or psychiatric disorders.

Language: Английский

Bioinformatic analysis and experimental validation of six cuproptosis-associated genes as a prognostic signature of breast cancer

PeerJ, Journal Year: 2024, Volume and Issue: 12, P. e17419 - e17419

Published: June 18, 2024

Breast carcinoma (BRCA) is a life-threatening malignancy in women and shows poor prognosis. Cuproptosis novel mode of cell death but its relationship with BRCA unclear. This study attempted to develop cuproptosis-relevant prognostic gene signature for BRCA. Cuproptosis-relevant subtypes were obtained by consensus clustering. Differential expression analysis was implemented using the 'limma' package. Univariate Cox multivariate analyses performed determine signature. The constructed validated distinct datasets. Gene set variation (GSVA) enrichment (GSEA) also conducted uncover underlying molecular mechanisms. ESTIMATE CIBERSORT algorithms applied probe linkage between tumor microenvironment (TME). Immunotherapy responsiveness assessed Tumor Immune Dysfunction Exclusion (TIDE) web tool. Real-time quantitative PCR (RT-qPCR) detect expressions genes breast cancer lines. Thirty-eight cuproptosis-associated differentially expressed (DEGs) mined clustering differential analysis. Based on univariate analyses, six genes, namely SAA1, KRT17, VAV3, IGHG1, TFF1, CLEC3A, establish corresponding external validation sets. GSVA GSEA showed that multiple cycle-linked immune-related pathways along biological processes associated results revealed significantly different TMEs two Cusig score subgroups. Finally, RT-qPCR lines further confirmed expressional trends CLEC3A. Taken together, we projecting overall survival patients our findings authenticated which are expected provide basis developing biomarkers an in-depth understanding cuproptosis

Language: Английский