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DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [ATAC-Seq]

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE169633 | GEO | 2022/07/29

REPOSITORIES: GEO

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DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [ATAC-Seq]

Project description:Squamous cell carcinomas (SCC) constitute a group of human malignancies that originate from the squamous epithelium. Most SCC patients experience treatment failure and relapse and have a poor prognosis due to de novo and acquired resistance to first-line chemotherapeutic agents. To identify chemoresistance mechanisms and explore novel targets for chemosensitization, we performed whole-transcriptome sequencing of paired resistant and parental SCC cells. We identified DLGAP1 antisense RNA 2 (D-AS2) as a crucial noncoding RNA that contributes to chemoresistance in SCC. Mechanistically, D-AS2 affected chromatin accessibility around the histone mark H3K27ac of FAM3 metabolism regulating signaling molecule D (FAM3D), reducing FAM3D mRNA transcription and extracellular protein secretion. FAM3D interacted with the Gαi-coupled G protein-coupled receptors (GPCRs) formyl peptide receptor 1 (FPR1) and FPR2 to suppress phospholipase D (PLD) activity, and reduced FAM3D increased PLD signaling. Moreover, activated PLD promoted phosphatidic acid (PA) production and subsequent nuclear translocation of yes-associated protein (YAP). Accordingly, in vivo administration of a D-AS2-targeting antisense oligonucleotide sensitized SCC to cisplatin treatment. In summary, this study shows that D-AS2/FAM3D-mediated PLD/PA lipid signaling is essential for SCC chemoresistance, suggesting D-AS2 can be targeted to sensitize SCC to cytotoxic chemotherapeutic agents.

2022-07-29 | GSE169502 | GEO

DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [RNA-Seq]

2022-07-29 | GSE169631 | GEO

DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [ATAC-Seq]

Project description:DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [ATAC-Seq]

| PRJNA716819 | ENA

DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [ATAC-Seq]

Project description:DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [ATAC-Seq]

| PRJNA717393 | ENA

DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [RNA-Seq]

Project description:DLGAP1-AS2-Mediated Phosphatidic Acid Synthesis Activates YAP Signaling and Confers Chemoresistance in Squamous Cell Carcinoma [RNA-Seq]

| PRJNA717398 | ENA

phosphatidic acid in gene expression-Phosphatidic acid in gene expression

Project description:au10-12_pa - phosphatidic acid in gene expression - Role of DGK in gene expression - Compounds were added 4h before cell harvesting. 6 dye-swap - treated vs untreated comparison

2012-03-01 | E-GEOD-35872 | biostudies-arrayexpress

phosphatidic acid in gene expression-Phosphatidic acid in gene expression

Project description:au10-12_pa - phosphatidic acid in gene expression - Role of DGK in gene expression - Compounds were added 4h before cell harvesting.

2012-03-01 | GSE35872 | GEO

Fusobacterium nucleatum confers chemoresistance by modulating autophagy in oesophageal squamous cell carcinoma.

Project description:BackgroundFusobacterium nucleatum (F. nucleatum) is a gut microbe implicated in gastrointestinal tumorigenesis. Predicting the chemotherapeutic response is critical to developing personalised therapeutic strategies for oesophageal cancer patients. The present study investigated the relationship between F. nucleatum and chemotherapeutic resistance in oesophageal squamous cell carcinoma (ESCC).MethodsWe examined the relationship between F. nucleatum and chemotherapy response in 120 ESCC resected specimens and 30 pre-treatment biopsy specimens. In vitro studies using ESCC cell lines and co-culture assays further uncovered the mechanism underlying chemotherapeutic resistance.ResultsESCC patients with F. nucleatum infection displayed lesser chemotherapeutic response. The infiltration and subsistence of F. nucleatum in the ESCC cells were observed by transmission electron microscopy and laser scanning confocal microscopy. We also observed that F. nucleatum modulates the endogenous LC3 and ATG7 expression, as well as autophagosome formation to induce chemoresistance against 5-FU, CDDP, and Docetaxel. ATG7 knockdown resulted in reversal of F. nucleatum-induced chemoresistance. In addition, immunohistochemical studies confirmed the correlation between F. nucleatum infection and ATG7 expression in 284 ESCC specimens.ConclusionsF. nucleatum confers chemoresistance to ESCC cells by modulating autophagy. These findings suggest that targeting F. nucleatum, during chemotherapy, could result in variable therapeutic outcomes for ESCC patients.

| S-EPMC7921654 | biostudies-literature

A Chemoenzymatic Strategy for Imaging Cellular Phosphatidic Acid Synthesis.

Project description:Phosphatidic acid (PA) is a potent lipid secondary messenger, the synthesis of which is tightly regulated in both space and time. Established tools for detecting PA involve ex vivo analysis and do not provide information on the subcellular locations where this lipid is synthesized. Here, a chemoenzymatic strategy for imaging sites of cellular PA synthesis by phospholipase D (PLD) enzymes is reported. PLDs were found to be able to catalyze phospholipid head-group exchange with alkynols to generate alkyne-labeled PA analogues within cells. Subsequent fluorophore tagging through Cu-catalyzed azide-alkyne cycloaddition enabled both visualization by fluorescence microscopy and quantification by HPLC. Our studies revealed several intracellular sites of PLD-mediated PA synthesis. We envision applications of this approach to dissect PA-dependent signaling pathways, image PLD activity in disease, and remodel intracellular membranes with new functionality.

| S-EPMC5153663 | biostudies-literature

PHOSPHATIDIC ACID SYNTHESIS IN YEAST.

Project description:1. The presence of palmitoyl-CoA-l-glycerol 1-phosphate palmitoyltransferase (EC2.3.1.15) has been demonstrated in a particulate fraction of baker's yeast. 2. The enzyme has been characterized, and its activity studied as a function of pH and concentration of substrates. 3. Inhibition by thiol poisons and protection by acyl-CoA have been used to obtain information on the active site. 4. By various methods of supplying acyl radicals, the species ;palmitoyl-CoA' has been shown to be the true acyl donor to the transferase.

| S-EPMC1206433 | biostudies-other

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