EGF and HRG, growth factor ligands for EGFR and ErbB3/4 receptor, induce transient and sustained ERK activity associated with cellular proliferation and differentiation of MCF-7 cells, respectively. To rigorously analyze the effect of ERK signal duration for mRNA expression dynamics and its relationship with cell determination, we modified the EGF-triggered ERK signal duration by changing the EGFR activation dynamics by impairing the ubiquitination and degradation process. Mutation of the six lysine residues (6KR; K692, K713, K730, K843, K905 and K946) of the EGFR responsible for ubiquitin conjugation has shown sustained phosphorylation of the receptor (Huang et al, 2006; Goh et al, 2010). Therefore we constructed the MCF-7 cell lines that stably express 6KR EGFR (6KR), and analyzed signaling and mRNA expression dynamics in response to EGF and HRG.
Feedforward regulation of mRNA stability by prolonged extracellular signal-regulated kinase activity.
Sex, Age, Specimen part, Disease, Cell line, Race, Time
View SamplesWe show that numerous miRNAs are transcriptionally up-regulated in papillary thyroid carcinoma (PTC) tumors compared with unaffected thyroid tissue. Among the predicted target genes of the three most upregulated miRNAs (miRs 221, 222 and 146b), only less than 15% showed significant downexpression in transcript level between tumor and unaffected tissue. The KIT gene which is known to be downregulated by miRNAs 221 and 222 displayed dramatic loss of transcript and protein in those tumors that had abundant mir-221, mir-222, and mir-146b transcript.
The role of microRNA genes in papillary thyroid carcinoma.
Specimen part
View SamplesmiR-155 transgenic mice develop pre-B cell leukemia/lymphoma. Though some targets of miR-155 are known, understanding of the mechanism by which miR-155 overexpression drives malignant transformation is not known. MicroRNAs regulate multiple genes.
miR-155 targets histone deacetylase 4 (HDAC4) and impairs transcriptional activity of B-cell lymphoma 6 (BCL6) in the Eμ-miR-155 transgenic mouse model.
No sample metadata fields
View SamplesWe present a microarray analysis of primary mouse astrocytes exposed to HIV-1 in culture. Results are compared with previous genomic studies of HIV-1 effect in human astrocytes and human and macaque brains.
Gene expression profiles of HIV-1-infected glia and brain: toward better understanding of the role of astrocytes in HIV-1-associated neurocognitive disorders.
Specimen part, Treatment
View SamplesNumerous studies have described the altered expression and the causal role of miRNAs in human cancer. However, to date efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here, we find that Nucleolin (NCL), a major nucleolar protein, post-transcriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, causally involved in breast cancer initiation, progression and drug-resistance. We also show that NCL is commonly overexpressed in human breast tumors, and its expression correlates with that of NCL-dependent miRNAs. Finally, this study indicates that NCL-binding guanosine-rich aptamers affect the levels of NCL-dependent miRNAs and their target genes, reducing breast cancer cell aggressiveness, both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer.
In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation.
Cell line
View SamplesInduced pluripotent stem cells (iPSCs) outwardly appear to be indistinguishable from embryonic stem cells (ESCs). A study of gene expression profiles of mouse and human ESCs and iPSCs suggests that, while iPSCs are quite similar to their embryonic counterparts, a recurrent gene expression signature appears in iPSCs regardless of their origin or the method by which they were generated. Upon extended culture, hiPSCs adopt a gene expression profile more similar to hESCs; however, they still retain a gene expression signature unique from hESCs that extends to miRNA expression. Genome-wide data suggested that the iPSC signature gene expression differences are due to differential promoter binding by the reprogramming factors. High-resolution array profiling demonstrated that there is no common specific subkaryotypic alteration that is required for reprogramming and that reprogramming does not lead to genomic instability. Together, these data suggest that iPSCs should be considered a unique subtype of pluripotent cell.
Induced pluripotent stem cells and embryonic stem cells are distinguished by gene expression signatures.
Specimen part, Cell line
View SamplesMutant embryos lacking maternal and zygotic HOW exhibit defects in mesoderm development. How is an RNA binding protein that regulates the levels of mRNAs by controling RNA metabolism.
Post-transcriptional repression of the Drosophila midkine and pleiotrophin homolog miple by HOW is essential for correct mesoderm spreading.
No sample metadata fields
View SamplesLong noncoding RNAs (lncRNAs) are transcripts longer than 200 nucleotides located within the intergenic stretches or overlapping antisense transcripts of protein coding genes. LncRNAs are involved in numerous biological roles including imprinting, epigenetic regulation, apoptosis and cell-cycle. To determine whether lncRNAs are associated with clinical features and recurrent mutations in older patients (aged =60 years) with cytogenetically normal (CN) acute myeloid leukemia (AML), we evaluated lncRNA expression in 148 untreated older CN-AML cases using a custom microarray platform. Overall design: In this study, we analyzed a large set of older CN-AML patients using custom lncRNA microarrays to investigate whether lncRNA expression is associated with clinical features, molecular abnormalities and outcome and to build a prognostic lncRNA signature that was subsequently validated using RNA sequencing. This submission represents RNA-Seq component of study.
Expression and prognostic impact of lncRNAs in acute myeloid leukemia.
No sample metadata fields
View SamplesAntiretroviral therapy (ART) has reduced morbidity and mortality in HIV infection; however HIV-1-associated neurocognitive disorders (HAND) persist despite treatment. We used microarray analysis in post-mortem brain tissues to determine ART effectiveness in the brain and to identify molecular signatures of HAND under ART.
Significant effects of antiretroviral therapy on global gene expression in brain tissues of patients with HIV-1-associated neurocognitive disorders.
Specimen part, Disease, Disease stage, Treatment
View SamplesLyme disease (LD), caused by Borrelia burgdorferi, is the most common tick-borne infectious disease in the United States. We examined gene expression patterns in the blood of individuals with early disseminated LD at the time of diagnosis (Acute LD) and also at approximately 1 month and 6 months following antibiotic treatment. A distinct acute LD profile was observed that was sustained during early convalescence (1 month) but returned to control levels six months after treatment. Using a computer learning algorithm, we identified sets of 20 classifier genes that discriminate LD from other bacterial and viral infections. In addition, these novel LD biomarkers are highly acurate in distinvuishing patients with acute LD from healthy subjects and in discriminating between individuals with active and resolved infecitons. This computational approach offers the potential for more accurate diagnosis of early dissminated Lyme disease. It may also allow improved monitoring of treatment efficacy and disease resolution.
Global Transcriptome Analysis Identifies a Diagnostic Signature for Early Disseminated Lyme Disease and Its Resolution.
Disease, Disease stage
View Samples