Primary mitochondrial respiratory chain (RC) diseases are heterogeneous in etiology and manifestations but collectively impair cellular energy metabolism. To identify a common cellular response to RC disease, systems biology level transcriptome investigations were performed in human RC disease skeletal muscle and fibroblasts. Global transcriptional and post-transcriptional dysregulation in a tissue-specific fashion was identified across diverse RC complex and genetic etiologies. RC disease muscle was characterized by decreased transcription of cytosolic ribosomal proteins to reduce energy-intensive anabolic processes, increased transcription of mitochondrial ribosomal proteins, shortened 5'-UTRs to improve translational efficiency, and stabilization of 3'-UTRs containing AU-rich elements. These same modifications in a reversed direction typified RC disease fibroblasts. RC disease also dysregulated transcriptional networks related to basic nutrient-sensing signaling pathways, which collectively mediate many aspects of tissue-specific cellular responses to primary RC disease. These findings support the utility of a systems biology approach to improve mechanistic understanding of mitochondrial RC disease.
Primary respiratory chain disease causes tissue-specific dysregulation of the global transcriptome and nutrient-sensing signaling network.
Sex, Age, Specimen part
View SamplesPAI-1 is considered as an oncogenic protein. However, PAI-1 deficiency didn’t stop tumor development in animal cancer models. Thus, it is suggested that there may be compensatory pathway that support tumor growth in the absence of PAI-1.
Plasminogen activator inhibitor-2 (PAI-2) overexpression supports bladder cancer development in PAI-1 knockout mice in N-butyl-N- (4-hydroxybutyl)-nitrosamine- induced bladder cancer mouse model.
Specimen part, Treatment
View SamplesWe aimed to identify a reprogramming factor in mammalian oocytes. DJ-1 is one candidate gene of the factor. Inhibition of DJ-1 function in nuclear transfer embryos affected developmental abilities. The downstream effect of this DJ-1 inhibition was examined using microarrays.
Identification and characterization of an oocyte factor required for development of porcine nuclear transfer embryos.
Disease
View SamplesTo clarify the downstream signal pathway of EML4-ALK in NSCLC, we performed Affymetrix GeneChip analysis using ALK inhibitor CH5424802-treated NCI-H2228 xenograft tumors, and comprehensively characterized the gene expression regulated by inhibition of activated ALK.
CH5424802, a selective ALK inhibitor capable of blocking the resistant gatekeeper mutant.
Specimen part
View SamplesCancer cells consume large amounts of glucose because of their specific metabolic pathway. However, cancer cells exist in tumor tissue where glucose is insufficient. To survive, cancer cells likely have the mechanism to elude their glucose addiction. Here we show that functional mitochondria are essential if cancer cells are to avoid glucose addiction.
Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions.
Disease, Cell line, Time
View SamplesThe differences of clinical characteristics in complex seizures induced by influenza A(H1N1)pdm09 and rotavirus gastroenteritis are well known, but the pathogenic mechanisms remain unclear. We analyzed the gene expression profiles in the peripheral whole blood cells isolated from pediatric patients using an Affymetrix oligonucleotide microarray.
Gene expression analysis in children with complex seizures due to influenza A(H1N1)pdm09 or rotavirus gastroenteritis.
Sex, Age, Specimen part, Disease, Disease stage, Subject
View SamplesTranscriptome analysis of post-mortem brain tissue specimens from three brain regions (BRs), entorinal, temporal and frontal cortices, of 71 Japanese brain-donor subjects to identify genes relevant to the expansion of neurofibrillary tangles. In total, 213 brain tissue specimens (= 71 subjects 3 BRs) were involved in this study. The spreading of neurofibrillary tangles (NFTs), intraneuronal aggregates of highly phosphorylated microtubule-associated protein tau, across the human brain is correlated with the cognitive severity of Alzheimers disease (AD). To identify genes relevant to NFT expansion defined by the Braak stage, we conducted exon array analysis with an exploratory sample set consisting of 213 human post-mortem brain tissue specimens from the entorinal, temporal and frontal cortices of 71 brain-donor subjects: Braak NFT stages 0 (N = 13), III (N = 20), IIIIV (N = 19) and VVI (N = 19). We identified eight genes, RELN, PTGS2, MYO5C, TRIL, DCHS2, GRB14, NPAS4 and PHYHD1, associated with the Braak stage. The expression levels of three genes, PHYHD1, MYO5C and GRB14, exhibited reproducible association on real-time quantitative PCR analysis. In another sample set, including control subjects (N = 30) and patients with late-onset AD (N = 37), dementia with Lewy bodies (N = 17) and Parkinson disease (N = 36), the expression levels of two genes, PHYHD1 and MYO5C, were obviously associated with late-onset AD. Proteinprotein interaction network analysis with a public database revealed that PHYHD1 interacts with MYO5C via POT1, and PHYHD1 directly interacts with amyloid beta-peptide 42. It is thus likely that functional failure of PHYHD1 and MYO5C could lead to AD development.
Genes associated with the progression of neurofibrillary tangles in Alzheimer's disease.
Sex, Specimen part, Subject
View SamplesWe isolated the meristematic and elongation zones of Col-0, upb1-1 mutant and 35S::UPB1-3YFP/upb1-1 plants by micro-dissection and extracted RNA from each section independently.
Transcriptional regulation of ROS controls transition from proliferation to differentiation in the root.
Age, Specimen part
View SamplesThe roles of histone demethylase KDM7 in gene expression were analyzed by gene expression profiling experiments with the mouse neuroblastoma cell line Neuro2A.
KDM7 is a dual demethylase for histone H3 Lys 9 and Lys 27 and functions in brain development.
Specimen part, Cell line
View SamplesTo examine the differences between NOR1 and its fusion gene product EWS/NOR1, we compared the gene expression profiles of NOR1- and EWS/NOR1-overexpressing 293 cells.
Differential transactivation by orphan nuclear receptor NOR1 and its fusion gene product EWS/NOR1: possible involvement of poly(ADP-ribose) polymerase I, PARP-1.
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