Childhood T-ALL samples were compared with thymocyte subsets
Deregulated WNT signaling in childhood T-cell acute lymphoblastic leukemia.
Specimen part
View SamplesCARM1 is an arginine methyltransferase that asymmetrically dimethylates protein substrates on arginine residues. CARM1 is often overexpressed in cancers and stimulates growth. However, clinically applicable therapeutic strategies based on CARM1 expression in cancer remains to be explored. Here we show that epithelial ovarian cancer is among the cancers with the highest CARM1 amplification rates that predicates a shorter survival. Our unbiased screen show that CARM1-expressing ovarian cancer cells are selectively sensitive to the inhibition of EZH2, another epigenetic regulator that silences its target genes. Inhibition of EZH2 activity using a clinically applicable small molecule inhibitor significantly suppressed the growth of CARM1-expressing ovarian tumors in two xenograft models. The observed selectivity correlates with upregulation of EZH2 target genes in a CARM1-dependent manner. CARM1 promotes EZH2 dependent gene silencing by methylating BAF155 to alter the antagonism between EZH2 and BAF155. Together, these results indicate that pharmacological inhibition of EZH2 is a novel therapeutic strategy for CARM1-expressing cancers. Overall design: CARM1 wild type and knockout samples assayed by RNA-seq
CARM1-expressing ovarian cancer depends on the histone methyltransferase EZH2 activity.
Cell line, Subject
View SamplesParathyroid hormone (PTH) plays an essential role in regulating calcium and bone homeostasis in the adult, but whether PTH is required at all for regulating fetal-placental mineral homeostasis is uncertain. To address this we treated Pth-null mice in utero with 1 nmol PTH (1-84) or saline and examined placental calcium transfer 90 minutes later. It was found that placental calcium transfer increased in Pth-null fetuses treated with PTH as compared to Pth-null fetuses treated with saline. Subsequently, to determine the effect of PTH treatment on placental gene expression, in a separate experiment, 90 minutes after the fetal injections the placentas were removed for subsequent RNA extraction and microarray analysis.
Parathyroid hormone regulates fetal-placental mineral homeostasis.
Sex, Specimen part, Treatment
View SamplesWe report high-throughput profiling of gene expression from whole zebrafish ventricles. We profile mRNA in uninjured ventricles and those undergoing regeneration 14 days after genetic ablation. This study provides a framework for understanding transcriptional changes during adult models of regeneration. Overall design: Examination of gene expression in cardiomyocytes under different states of proliferation.
Resolving Heart Regeneration by Replacement Histone Profiling.
No sample metadata fields
View SamplesOverexpression of ecotropic viral integration site 1 (EVI1) is associated with aggressive disease in acute myeloid leukemia (AML). Despite of its clinical importance, little is known about the mechanism through which EVI1 confers resistance to antileukemic drugs. Here, we show that a human myeloid cell line constitutively overexpressing EVI1 after infection with a retroviral vector (U937_EVI1) was partially resistant to etoposide and daunorubicin as compared to empty vector infected control cells (U937_vec). Similarly, inducible expression of EVI1 in HL-60 cells decreased their sensitivity to daunorubicin. Gene expression microarray analyses of U937_EVI1 and U937_vec cells cultured in the absence or presence of etoposide showed that 77 and 419 genes were regulated by EVI1 and etoposide, respectively. Notably, mRNA levels of 26 of these genes were altered by both stimuli, indicating that EVI1 regulated genes were strongly enriched among etoposide regulated genes and vice versa. One of the genes that were induced by both EVI1 and etoposide was CDKN1A/p21/WAF, which in addition to its function as a cell cycle regulator plays an important role in conferring chemotherapy resistance in various tumor types. Indeed, overexpression of CDKN1A in U937 cells mimicked the phenotype of EVI1 overexpression, similarly conferring partial resistance to antileukemic drugs.
EVI1 inhibits apoptosis induced by antileukemic drugs via upregulation of CDKN1A/p21/WAF in human myeloid cells.
Cell line, Treatment
View SamplesWe used microarrays to identify transcripts regulated by dexamethasone in omental (Om) and abdominal subcutaneous (Abdsc) adipose tissues of severely obese females obtained during elective surgeries.
Depot Dependent Effects of Dexamethasone on Gene Expression in Human Omental and Abdominal Subcutaneous Adipose Tissues from Obese Women.
Specimen part, Disease stage, Treatment
View SamplesPurpose: The goal of this study is to analyze the transcriptional pathways regulated by Fbxo22 and Keap1 in mouse lung adeno carcinoma cells. Methods: mouse lung adeno carcinoma cells either Keap1 wild type (KP) or mutant (KPK), have been transfected for 3 days with siRNA targeting Fbxo22. Knock down efficiency has been evaluated by western blot (using specific antibody for Fbxo22) and qPCR (using specific oligos for Fbxo22) . Results: The transcriptomic analysis helps us to support our finding that loss of either Keap1 or Fbxo22 induces metastases Overall design: All 12 samples generated by deep sequencing in triplicate
Nrf2 Activation Promotes Lung Cancer Metastasis by Inhibiting the Degradation of Bach1.
Specimen part, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Specimen part, Treatment
View SamplesMammalian insulin and IGF induce similar but not identical changes in gene expression downstream of their respective receptors. Signaling bias at the receptor differentiates the two similar ligands, though the precise mechanism is not entirely understood. We used Drosophila insulin-like peptides DILP2 and DILP5 to determine how similar insulin-like ligands regulate similar and distinct patterns of gene expression in S2 cells by RNA-Seq. Overall, DILP2 and DILP5 stimulate many of the same changes in gene expression. However, some genes are uniquely regulated by DILP2 or by DILP5. Shared and distinct gene targets were validated by q-RT-PCR with indepedent replicates. Some unique gene targets of DILP2 are involved in sugar metabolism, which is functionally related in vivo to DILP2 and not DILP5. We find that gene expression is largely regulated in parallel by DILP2 and DILP5 but some key unique targets may lead to differential physiological functions for the two insulin-like genes. Overall design: mRNA profiles from S2 cells treated with DILP2, DILP5 or solvent were sequenced on an Illumina HiSeq2500
<i>Drosophila</i> Insulin-Like Peptides DILP2 and DILP5 Differentially Stimulate Cell Signaling and Glycogen Phosphorylase to Regulate Longevity.
Cell line, Treatment, Subject
View SamplesMicroRNA-offset RNAs (moRs) were first identified in simple chordates and subsequently in mouse and human cells by deep sequencing of short RNAs. MoRs are derived from sequences located immediately adjacent to microRNAs (miRs) in the primary miR (pri-miR). Currently moRs are considered to be simply a by-product of miR biosynthesis that lack biological activity. Here we show for the first time that a moR is biologically active. We now demonstrate that endogenous and over-expressed moR-21 significantly alters gene expression and inhibits the proliferation of vascular smooth muscle cells (VSMC). We report that the seed region of moR-21 as well as the seed match region in the target gene 3'UTR are indispensable for moR-21-mediated gene down-regulation. We further demonstrated that moR-21-mediated gene repression is Argonaute 2 (Ago2) dependent. In addition, we find that miR-21 and moR-21 may regulate different genes in a given pathway and can oppose each other in regulating certain genes. Taken together, these findings provide the first evidence that microRNA offset RNA regulates gene expression and is biologically active.
MicroRNA-Offset RNA Alters Gene Expression and Cell Proliferation.
Specimen part, Treatment
View Samples