Transcriptome analysis of MET-constitutively active versus MET-silenced colorectal cancer cells
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE212835 | GEO | 2023/10/14
REPOSITORIES: GEO
Similar Datasets
Project description:TCPOBOP (1,4-Bis [2-(3,5-Dichloropyridyloxy)] benzene) is a constitutive androstane receptor (CAR) agonist that induces robust hepatocyte proliferation and hepatomegaly without any liver injury or tissue loss. TCPOBOP-induced direct hyperplasia has been considered to be CAR-dependent with no evidence of involvement of cytokines or growth factor signaling. Receptor tyrosine kinases (RTKs), MET and EGFR, are known to play a critical role in liver regeneration after partial hepatectomy, but their role in TCPOBOP-induced direct hyperplasia, not yet explored, is investigated in the current study. Disruption of the RTK-mediated signaling was achieved utilizing MET KO mice along with Canertinib treatment for EGFR inhibition. Combined elimination of MET and EGFR signaling [MET KO + EGFRi], but not individual disruption, dramatically reduced TCPOBOP-induced hepatomegaly and hepatocyte proliferation. TCPOBOP-driven CAR activation was not altered in [MET KO + EGFRi] mice, as measured by nuclear CAR translocation and analysis of typical CAR target genes. However, TCPOBOP induced cell cycle activation was impaired in [MET KO + EGFRi] mice due to defective induction of cyclins, which regulate cell cycle initiation and progression. TCPOBOP-driven induction of FOXM1, a key transcriptional regulator of cell cycle progression during TCPOBOP-mediated hepatocyte proliferation, was greatly attenuated in [MET KO + EGFRi] mice. Interestingly, TCPOBOP treatment caused transient decline in HNF4α expression concomitant to proliferative response; this was not seen in [MET KO + EGFRi] mice. Transcriptomic profiling revealed vast majority (~40%) of TCPOBOP-dependent genes mainly related to proliferative response, but not to drug metabolism, were differentially expressed in [MET KO + EGFRi] mice. Conclusion: Taken together, combined disruption of EGFR and MET signaling lead to dramatic impairment of TCPOBOP-induced proliferative response without altering CAR activation. We used microarrays to detail the global programme of gene expression in [METKO + EGFRi] mice liver following TCPOBOP treatment
2018-08-28 | GSE110695 | GEO
Project description:We have previously shown that deprivation of essential amino acids, namely methionine/cysteine or tyrosine, leads to the transcriptional reactivation of integrated silenced transgenes, and latent HIV-1 provirus. In an effort to understand the underlying mechanisms, here we investigate the overall transcriptional profile of HeLa cells upon Met/Cys starvation for different time points, including the expression of repeated and transposable elements. HeLa cells carrying a stably integrated and silenced plasmid expressing the OA1/GPR143 gene (pcDNA3.1-OA1) were cultured in regular DMEM medium for 6-30-120 hours, or in absence of Met/Cys for 6-15-30-72-120 hours, and the changes in the expression of genes and repeated elements was evaluated by RNAseq
2018-07-21 | E-MTAB-6452 | biostudies-arrayexpress
Project description:The placenta serves as the structural interface for nutrient and waste exchange for proper fetal development. Although defects in placental function result in various placental disorders, molecular mechanisms orchestrating placental development and function are poorly understood. Gene targeting studies have shown that Hgf or c-Met KO embryos exhibit growth retardation and markedly smaller size of the placenta, and die by E14.5. Stem/progenitor cells in various tissues express c-Met and they participate in morphogenesis and tissue repair. Thus, we hypothesized that the HGF/c-Met signaling pathway is essential for the emergence, proliferation, and/or differentiation of putative stem/precursor cells of labyrinth trophoblasts at the midgestation stage. To examine the downstream mechanisms of HGF/c-Met signaling pathway that regulate placental labyrinth development, we performed microarray analysis and compared the transcriptional profiles of wild-type and c-Met g-KO placentas. The highly enriched gene ontology categories among the transcripts that were down-regulated in the mutant placentas were related to cell cycle, transcription, and placenta development. Surprisingly, the most highly enriched GO category among the up-regulated genes was immune response. Furthermore, genes classified as “unsaturated fatty acid metabolic process” were also significantly enriched among the up-regulated genes. This expression data suggested that HGF/c-Met signaling pathway positively regulates progression of cell cycle and transcription of placenta specific genes, and negatively regulates inflammatory reaction and fatty acids synthesis in the trophoblasts, thereby coordinating many critical cellular processes in the placenta. Freshly harvested mouse placental trophoblast was enriched for CD9 from wild -type and c-Met KO placenta with 2 independent biological replicates
2013-12-31 | E-GEOD-38342 | biostudies-arrayexpress
Project description:Packaging genomic regions into silenced heterochromatin is critical to maintain organismal viability and tissue identity. Methylation of histone H3 on lysine 9 (H3K9me) marks heterochromatin. Here we show that in addition to catalyzing H3K9me, the C. elegans histone methyltransferase MET-2 (SETDB1-like) has a second non-catalytic function that can itself contribute to gene repression. We find that subnuclear concentrates, or foci, of MET-2 correlate with efficient HMT activity, yet foci composed of catalytic-deficient MET-2 are also able to mediate transcriptional silencing. Genetic ablation of met-2 or physiological disruption of MET-2 foci by heat stress results in loss of silencing coincident with an increase in histone acetylation. Restoration of catalytically deficient MET-2 foci mitigates H3K9 and H3K27 hyperacetylation, gene derepression, and infertility, demonstrating a structural role for foci of a conserved heterochromatic histone methyltransferase in gene silencing independent of its enzymatic activity.
2021-08-01 | GSE168924 | GEO
Project description:Packaging genomic regions into silenced heterochromatin is critical to maintain organismal viability and tissue identity. Methylation of histone H3 on lysine 9 (H3K9me) marks heterochromatin. Here we show that in addition to catalyzing H3K9me, the C. elegans histone methyltransferase MET-2 (SETDB1-like) has a second non-catalytic function that can itself contribute to gene repression. We find that subnuclear concentrates, or foci, of MET-2 correlate with efficient HMT activity, yet foci composed of catalytic-deficient MET-2 are also able to mediate transcriptional silencing. Genetic ablation of met-2 or physiological disruption of MET-2 foci by heat stress results in loss of silencing coincident with an increase in histone acetylation. Restoration of catalytically deficient MET-2 foci mitigates H3K9 and H3K27 hyperacetylation, gene derepression, and infertility, demonstrating a structural role for foci of a conserved heterochromatic histone methyltransferase in gene silencing independent of its enzymatic activity.
2021-08-01 | GSE168923 | GEO
Project description:The placenta serves as the structural interface for nutrient and waste exchange for proper fetal development. Although defects in placental function result in various placental disorders, molecular mechanisms orchestrating placental development and function are poorly understood. Gene targeting studies have shown that Hgf or c-Met KO embryos exhibit growth retardation and markedly smaller size of the placenta, and die by E14.5. Stem/progenitor cells in various tissues express c-Met and they participate in morphogenesis and tissue repair. Thus, we hypothesized that the HGF/c-Met signaling pathway is essential for the emergence, proliferation, and/or differentiation of putative stem/precursor cells of labyrinth trophoblasts at the midgestation stage. To examine the downstream mechanisms of HGF/c-Met signaling pathway that regulate placental labyrinth development, we performed microarray analysis and compared the transcriptional profiles of wild-type and c-Met g-KO placentas. The highly enriched gene ontology categories among the transcripts that were down-regulated in the mutant placentas were related to cell cycle, transcription, and placenta development. Surprisingly, the most highly enriched GO category among the up-regulated genes was immune response. Furthermore, genes classified as “unsaturated fatty acid metabolic process” were also significantly enriched among the up-regulated genes. This expression data suggested that HGF/c-Met signaling pathway positively regulates progression of cell cycle and transcription of placenta specific genes, and negatively regulates inflammatory reaction and fatty acids synthesis in the trophoblasts, thereby coordinating many critical cellular processes in the placenta.
2013-12-31 | GSE38342 | GEO
Project description:B16-F10 malignant mouse melanoma cells have been frequently used as highly metastatic cells. Based on heterogenous cell surface expression of Met/HGF (hepatocyte growth factor) receptor in B16-F10 cells, the cells were divided into Met-low and Met-high cells by flow cytometry and these populations were subjected to microarray analysis. Met-low and Met-high cells showed different expression profiles in genes involved characteristics of tumors, including stem cell maintenance, pigmentation, and angiogenesis.
2016-09-25 | GSE69741 | GEO
Project description:Using RNA-seq to explore the mechanisms underlysing the effects of methionyl-methionine dipeptide (Met-Met) or free methionine (Met) supplementation in Met-restricted mice during pregnancy on mammogenesis and lactation.
2022-04-02 | GSE129224 | GEO
Project description:SILAC analysis of scramble and gigaxonin silenced dorsal root ganglia cultures
2023-04-20 | MSV000091762 | MassIVE
Project description:To identify HGF/Met regulated genes, we performed expression microarray analysis after inducible activation of Met receptor in primary cultures of hepatocytes established from wild-type control (Alb-Cre +/-) and Met conditional knockout mice (Alb-Cre +/-; Met Fl/Fl). Keywords: time series design
2006-10-02 | GSE4451 | GEO