Regulation of gene expression at the post-transcriptional level plays an indispensable role during TGFbeta-induced EMT and metastasis. This regulation involves a transcript-selective translational regulatory pathway in which a ribonucleoprotein (mRNP) complex, consisting of heterogeneous nuclear ribonucleoprotein E1 (hnRNP E1) and eukaryotic elongation factor 1A1 (eEF1A1), binds to a 3-UTR regulatory BAT (TGF activated translation) element and silences translation of Dab2 and ILEI mRNAs, two transcripts which are involved in mediating EMT. TGFbeta activates a kinase cascade terminating in the phosphorylation of hnRNP E1, by isoform-specific stimulation of protein kinase B/Akt2, inducing the release of the mRNP complex from the 3-UTR element, resulting in the reversal of translational silencing and increased expression of Dab2 and ILEI transcripts.
Establishment of a TGFβ-induced post-transcriptional EMT gene signature.
Specimen part
View SamplesHPV E6 from the genus alpha 'high risk' types such as HPV16 recruit the ubiquitin ligase E6AP to ubiquitinate p53 and target it for proteasome-mediated degradation. This results in the functional inactivation of p53 in HPV16-E6 expressing cells.
Genus beta human papillomavirus E6 proteins vary in their effects on the transactivation of p53 target genes.
Specimen part, Cell line
View SamplesIdiopathic pulmonary fibrosis (IPF) and non-specific interstitial pneumonia (NSIP) are the 2 most common forms of idiopathic interstitial pneumonia. Response to therapy and prognosis are remarkably different. The clinical-radiographic distinction between IPF and NSIP may be challenging. We sought to investigate the gene expression profile of IPF vs. NSIP
Comprehensive gene expression profiling identifies distinct and overlapping transcriptional profiles in non-specific interstitial pneumonia and idiopathic pulmonary fibrosis.
Specimen part, Disease, Disease stage
View SamplesStudy the training exercise effects in chronic obstructive pulmonary disease (COPD) patients and aged-matched healthy individuals. Skeletal muscle biopsies from 9 stable COPD patients with normal fat free mass index (FFMI, 21Kg/m2) (COPDN), 6 COPD patients with low FFMI (16Kg/m2) (COPL), and 12 healthy sedentary subjects (FFMI 21Kg/m2) before and after 8 weeks of a supervised endurance exercise program were analyzed.
A systems biology approach identifies molecular networks defining skeletal muscle abnormalities in chronic obstructive pulmonary disease.
Specimen part, Disease, Disease stage, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences.
Specimen part
View SamplesUpon G1-S transition, cyclin-dependent kinases (CDKs) phosphorylate the retinoblastoma tumor suppressor protein (pRB) to release E2F transcription factors, which activate transcriptional programs, required for S-phase entry. Beyond the G1-S transition, pRB activity remains poorly understood. Our lab has discovered that pRB retains exclusive binding to E2F1 through an alternate E2F1-specific binding site at the pRB c-terminus independent of CDK phosphorylation. We have developed a gene-targeted mouse model that is defective for the E2F1-specific interaction. We are exploring the function of this complex through genome-wide binding and expression profiling. Overall, this work suggests an alternate pRB-E2F1 complex persists independent of CDK phosphorylation to establish regions of constitutive heterochromatin
An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences.
Specimen part
View SamplesUpon G1-S transition, cyclin-dependent kinases (CDKs) phosphorylate the retinoblastoma tumor suppressor protein (pRB) to release E2F transcription factors, which activate transcriptional programs, required for S-phase entry. Beyond the G1-S transition, pRB activity remains poorly understood. Our lab has discovered that hyperphosphorylated pRB (ppRB), found beyond G1, retains exclusive binding to E2F1 through an alternate E2F1-‘specific’ binding site at the pRB c-terminus. We have developed a gene-targeted mouse model that is defective for the E2F1-‘specific’ interaction. We are exploring the function of this complex through genome-wide expression profiling. Overall, this work suggests an alternate pRB-E2F1 complex persists beyond the G1-S transition to establish regions of constitutive heterochromatin. Overall design: 1. Total RNA from passage 4 quiescent MEFs isolated using TRIzol RNA extraction protocol 2. rRNA was depleted from total RNA using the RiboMinus Euk System V2 protocol according to manufacturer’s procotol 3. rRNA-depleted RNA samples were submitted for picoanalyzer analysis to determine concentration, purity, and rRNA content 4. Three wild-type and three mutant RNA samples with <10% rRNA remaining were submitted for library construction 5. Library was used for Illumina HiSeq 2500 paired end sequencing.
An RB-EZH2 Complex Mediates Silencing of Repetitive DNA Sequences.
No sample metadata fields
View SamplesTo determine if EP400 knockdown would affect Max target genes in Merkel cell carcinoma cell line MKL-1, we performed RNA-seq analyses of MKL-1 cells inducibly expressing EP400 shRNA and compared to ChIP-seq data using BETA analyses. Overall design: EP400 was inducibly reduced with shRNA in MKL-1 cells to analyze gene regulation.
Merkel cell polyomavirus recruits MYCL to the EP400 complex to promote oncogenesis.
No sample metadata fields
View SamplesThirty-eight tumors from 17 patients treated with BRAF inhibitor (n=12) or combination BRAF/MEK inhibitors (n=5) with known PD-L1 expression were analyzed. RNA expression arrays were performed on all pre-treatment (PRE, n=17), early during treatment (EDT, n=8) and progression (PROG, n=13) biopsies. HLA-A/HLA-DPB1 expression was assessed by immunohistochemistry (IHC). Gene set enrichment analysis (GSEA) of PRE, EDT and PROG melanomas revealed that transcriptome signatures indicative of immune cell activation were strongly positively correlated with PD-L1 staining. In contrast, MAPK signaling and canonical Wnt/--catenin activity were negatively associated with PD-L1 melanoma expression. The expression of PD-L1 and immune activation signatures did not simply reflect the degree or type of immune cell infiltration, and was not sufficient for tumor response to MAPK inhibition.
PD-L1 Expression and Immune Escape in Melanoma Resistance to MAPK Inhibitors.
Specimen part
View SamplesThe aim was to carry out global analysis of gene expression changes occurring in the normal pubertal mouse mammary gland from the appearance to the regression of terminal end buds.
ERalpha-CITED1 co-regulated genes expressed during pubertal mammary gland development: implications for breast cancer prognosis.
Sex, Age, Specimen part
View Samples