Gene Expression Analysis of the response to ACC inhibition
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA625957 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:BACKGROUND & AIMS: Nonalcoholic steatohepatitis (NASH) is a chronic liver disease characterized by hepatic lipid accumulation, inflammation, and progressive fibrosis. Acetyl-CoA carboxylase (ACC) catalyzes the rate-limiting step of de novo lipogenesis and regulates fatty-acid beta-oxidation in hepatocytes. ACC inhibition reduces hepatic fat content and markers of liver injury in NASH patients; however, the effect of ACC inhibition on liver fibrosis has not been reported. METHODS: A direct role for ACC in fibrosis was evaluated by measuring de novo lipogenesis, procollagen production, gene expression, glycolysis, and mitochondrial respiration in hepatic stellate cells (HSCs) in the absence or presence of small-molecule inhibitors of ACC. ACC inhibitors were evaluated in rodent models of liver fibrosis induced by diet or the hepatotoxin, DEN. Fibrosis and hepatic steatosis were evaluated by histological and biochemical assessments. RESULTS: In TGF-beta-stimulated HSCs, ACC inhibition reduced activation and collagen production independent of mitochondrial beta-oxidation by blocking de novo lipogenesis. ACC inhibition prevented a metabolic switch necessary for induction of glycolysis and oxidative phosphorylation during HSC activation. Consistent with this direct anti-fibrotic mechanism in HSCs, ACC inhibition reduced liver fibrosis in a rat CDHFD model and in response to chronic DEN-induced liver injury that lacked hepatic lipid accumulation. CONCLUSIONS: In addition to reducing lipid accumulation in hepatocytes, ACC inhibition also directly impairs the pro-fibrogenic activity of HSCs. Small molecule inhibitors of ACC may reduce liver fibrosis by both reducing lipotoxicity in hepatocytes and directly reducing HSC activation, providing a mechanistic rationale for the treatment of patients with advanced liver fibrosis due to NASH.
2020-04-24 | GSE148849 | GEO
Project description:Gene expression analysis in response to hypoxic pathway inhibition
| PRJNA494075 | ENA
Project description:The MYB-NFIB gene is a driver-mutation in the majority of adenoid cystic carcinomas (ACCs) and believed to control a large number of genes involved in tumorigenesis. This experiment investigates the effects on gene expression after siRNA knock-down of MYB-NFIB and/or inhibition of IGF1R/INSR signaling in ACC cells.
2018-06-01 | GSE76094 | GEO
Project description:Canola plants inoculated with plant growth-promoting bacteria either expressing ACC deaminase or not to determine the effect on plant gene expression using an Arabidopsis microarray.
2011-11-01 | GSE31396 | GEO
Project description:Adenoid cystic carcinoma (ACC) is an uncommon malignant neoplasm (incidence of 0.35 per 100,000) that occurs in different body sites. It most often arises in salivary glands and other secretory glands in the head and neck region. To find the gene expression signatures of ACC, we performed microarray experiments to compare ACC xenograft tumor models and normal tissue samples. We used microarrays to detail the global program of gene expression underlying adenoid cystic carcinoma and identified distinct classes of up- and down-regulated genes compared to non-neoplastic salivary tissue.
2012-03-27 | GSE36820 | GEO
Project description:Chromobox (CBX) family proteins are components in polycomb repressive complex 1 (PRC1), responsible for targeting PRC1 to the chromatin. We studied genes regulated by CBX6, 7, or 8 in human ACC-Meso-4 mesothelioma cell line by microarray analysis of ACC-Meso-4 cells stably expressing short hairpin RNA (shRNA) targeting CBX-6, 7, 8, or control nontarget shRNA.
2019-02-22 | GSE126605 | GEO
Project description:Adrenocortical carcinoma (ACC) is a rare endocrine malignancy accounting for between 0.02 and 0.2 percent of all cancer deaths. Surgical removal offers the only current potential for cure. Unfortunately, ACC has undergone metastatic spread in approximately 40-70 percent of patients at the time of diagnosis. Standard chemotherapy with mitotane containing regimens is often ineffective and associated with intolerable side-effects. Modern molecular technologies now allow the examination of germ-line and somatic DNA for chromosomal alterations which can give biological insight into cancer processes. Using an array-based high density comparative genomic hybridization (CGH) screen, genomic aberrations within 25 ACC patients were assessed to identify genomic characteristic of this cancer. Genomes were queried with >44,000 probes on the Agilent Human Genome CGH array detecting regions of chromosomal gain and loss within the tumor population. Statistical analysis of this genetic landscape reveals a set of chromosomal aberrations strongly associated with survival in an accumulation dependent fashion. These regions may hold prognostic indicators and offer therapeutic targets that can be used to develop novel treatments for aggressive tumors. Keywords: CGH, adrenocortical carcinoma, cancer
2007-04-10 | GSE7482 | GEO
Project description:Adrenocortical carcinomas (ACCs) are rare and aggressive endocrine cancers of the adrenal gland. Recently, a subtype of ACC characterized by a CpG island methylator phenotype (CIMP), associated with especially poor diagnosis, has been discovered. The purpose of this study is to investigate the role of DNA methylation and the impact on demethylating agent 5-azacytidine in ACC tumors aggressiveness. To this aim, we generated RRBS and RNAseq data from two ACC and one non-tumour cell lines treated or not with 5-azacytidine. We showed that CIMP has a direct impact on the aggressiveness of tumors through two main mechanisms; (1) by increasing survival and proliferation and (2) by favoring the tumor immune escape. These two mechanisms could at least partially be reversed upon 5-azacytidine treatment. Overall, our results show that strongly suggest that the co-treatment with demethylating agents to enhance the efficacy of immunotherapy could be beneficial for patients with high CIMP ACC.
2023-02-19 | GSE145560 | GEO
Project description:Individualized outcome prediction classifiers were successfully constructed through expression profiling of 1918 genes connected with lipid metabolism in yeast strain overexpressed of fatty acid biosynthesis gene In the study presented here, expression profiles of wild type and ACC-overexpressed wild type yeast strain were well-clustered by profiles- and gene similarities. It was analyzed the gene expression profile of ACC-overexpressing as compared with those of wild type. The expression levels between wild type(WT) and ACC-overexpressed wild type(ACC) were compared individually three times.
2012-01-13 | E-GEOD-35041 | biostudies-arrayexpress
Project description:This experiment investigates differences in global gene expression between ACC and NSG.
2018-06-01 | GSE88804 | GEO