Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA393976 | ENA |
REPOSITORIES: ENA
Similar Datasets
Project description:siRNA Administration Against AFP Inhibits Hepatocellular Carcinoma Proliferation in Vitro and Progression in Mice
| PRJNA113613 | ENA
Project description:Individuals expressing alpha-1-antitrypsin mutant Z protein accumulate misfolded, mutant protein in the liver and are at risk for liver diseases including cirrhosis and hepatocellular carcinoma. Transgenic PiZ mice, a model for this liver disease, display similar pathologies to humans, including inflammation, increases in proliferation, autophagy and apoptosis, accumulation of globules and develop fibrosis and hepatocellular carcinoma with age. Microarrays were used to compare the gene expressions of PiZ mice to wild-type mice in order to identify the pathways that are altered in this disorder. Pooled samples from 4 mice, 3-4 months old were used for each of 4 categories. PiZ males, PiZ females, C57Bl/6 males, C57Bl/6 females
2012-11-08 | E-GEOD-36478 | biostudies-arrayexpress
Project description:Individuals expressing alpha-1-antitrypsin mutant Z protein accumulate misfolded, mutant protein in the liver and are at risk for liver diseases including cirrhosis and hepatocellular carcinoma. Transgenic PiZ mice, a model for this liver disease, display similar pathologies to humans, including inflammation, increases in proliferation, autophagy and apoptosis, accumulation of globules and develop fibrosis and hepatocellular carcinoma with age. Microarrays were used to compare the gene expressions of PiZ mice to wild-type mice in order to identify the pathways that are altered in this disorder.
2012-11-08 | GSE36478 | GEO
Project description:Transforming growth factor beta-activated kinase1 (TAK1) encoded by the gene MAP3K7 regulates multiple important downstream effectors involved in immune response, cell death and carcinogenesis. Hepatocyte-specific deletion of TAK1 in Tak1_Hep mice promotes liver fibrosis and hepatocellular carcinoma (HCC) formation. Here, we report that genetic inactivation of RIPK1 kinase using kinase dead knock-in D138N mutation in Tak1_Hep mice inhibits the expression of liver tumor biomarkers, liver fibrosis and HCC formation. Inhibition of RIPK1, however, has no or minimum effect on hepatocyte loss and compensatory proliferation, which are the recognized factors important for liver fibrosis and HCC development. Using single cell RNA-seq, we discover that inhibition of RIPK1 strongly suppresses inflammation induced by hepatocyte-specific loss of TAK1. Activation of RIPK1 promotes the transcription of key proinflammatory cytokines, such as CCL2, and CCR2+ macrophage infiltration. Our study demonstrates the role and mechanism of RIPK1 kinase in promoting inflammation, both cell-autonomously and cell-non-autonomously, in the development of liver fibrosis and HCC, independent of cell death and compensatory proliferation. We suggest the possibility of inhibiting RIPK1 kinase as a therapeutic strategy for reducing liver fibrosis and HCC development by inhibiting inflammation.
2020-07-08 | GSE148859 | GEO
Project description:hepatocellular carcinoma vs. corresponding noncancerous liver or normal liver
| PRJNA95273 | ENA
Project description:Hepatic stellate cells (HSC) play critical roles in liver fibrosis and hepatocellular carcinoma (HCC). Vitamin D receptor (VDR) activation in HSC inhibits liver inflammation and fibrosis. Here we show that p62/SQSTM1, a protein that is upregulated in liver parenchymal cells but downregulated in HCC-associated HSC, negatively regulates HSC activation. Total body or HSC-specific p62 ablation potentiates HSC activation and enhances inflammation, fibrosis and HCC progression. We demonstrate that p62 directly interacts with VDR and RXR promoting their heterodimerization, which is critical for VDR:RXR target genes recruitment. Loss of p62 in HSC impairs the repression of fibrosis and inflammation by VDR agonists. This demonstrates that p62 is a negative regulator of liver inflammation and fibrosis through its ability to promote VDR signaling in HSC, whose activation supports HCC development.
2016-11-23 | GSE78760 | GEO
Project description:Mdr2 is the transporter of phosphatidylcholine, which is an essential component of bile. Deficiency of mdr2 causes hepatic inflammation, liver fibrosis and hepatocellular carcinoma. Mdr2-/- MEFs show increased proliferation, spontaneous transformation and tumorigenesis. We used microarray to obtain genome-wide profiling of gene expression underlying the changes in mdr2-/- MEFs.
2015-09-02 | GSE72615 | GEO
Project description:Mdr2 is the transporter of phosphatidylcholine, which is an essential component of bile. Deficiency of mdr2 causes hepatic inflammation, liver fibrosis and hepatocellular carcinoma. Mdr2-/- MEFs show increased proliferation, spontaneous transformation and tumorigenesis. We used microarray to obtain genome-wide profiling of gene expression underlying the changes in mdr2-/- MEFs. MEFs derived from wt and mdr2-/- littermate embyos were subjected to passage according to 3T3 protocols. RNA was extracted from cells on passage 40 and hybridized on Affymetrix microarrays.
2015-09-02 | E-GEOD-72615 | biostudies-arrayexpress