LIN28B is overexpressed in specific subtypes of pediatric leukemia and regulates lncRNA H19
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Hetty Helsmoortel
PROVIDER: E-GEOD-79981 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:The stem cell gene LIN28B was recently shown to be overexpressed in a foetal-like subgroup of juvenile myelomonocytic leukaemia. Given the involvement of LIN28B in a variety of solid paediatric cancers, we conducted a meta-analysis of LIN28B levels using publicly available gene expression data of 1361 paediatric leukaemia samples. Interestingly, this analysis revealed LIN28B overexpression in 102 childhood leukaemia patients (7.5%), suggesting oncogenic activity for LIN28B in the context of paediatric haematological diseases. As the mode of action of LIN28B during normal and malignant haematopoiesis remains largely unexplored, we subsequently analysed the transcriptional consequences of LIN28B modulation on normal and malignant haematopoietic cells and identified the long non-coding RNA (lncRNA) H19 as the first LIN28B-regulated lncRNA. Oci-AML3 cells were retrovirally transduced with MSCV-PIG-LIN28B and MSCV-PIG-empty vectors (gifts from Johua Mendel lab), selected with puromycin and hybridized on Agilent microarray.
2016-04-07 | E-GEOD-79979 | biostudies-arrayexpress
Project description:We sought to elucidate functions of LIN28B and potential mechanisms whereby it may promote metastasis by comparing the gene expression profile of LIN28B metastases to primary tumors. Accordingly, we performed microarray analysis on total RNA isolated from empty vector tumors, LIN28B-LoVo tumors, and LIN28B-LoVo metastases Constitutive LIN28B expression was achieved in the LoVo (ATCC #CCL-229) colon cancer cell line via retroviral transduction of MSCV-PIG-LIN28B. xenografts were produced via injection of 1x106 cells subcutaneously into the rear flanks of nude mice. Microarrays were conducted on primary tumors from empty vector and LIN28B-expressing cells, as well as metastases derived from primary tumors constitutively expressing LIN28B. (Note: metastases did not occur with empty vector tumors)
2010-12-29 | E-GEOD-26335 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the following subset Series: GSE26334: Expression data from LoVo colon cancer lines +/- constitutive LIN28B expression GSE26335: Expression data from xenograft tumors derived from LoVo colon cancer lines +/- constitutive LIN28B expression Refer to individual Series
2010-12-29 | E-GEOD-26336 | biostudies-arrayexpress
Project description:The stem cell gene LIN28B was recently shown to be overexpressed in a foetal-like subgroup of juvenile myelomonocytic leukaemia. Given the involvement of LIN28B in a variety of solid paediatric cancers, we conducted a meta-analysis of LIN28B levels using publicly available gene expression data of 1361 paediatric leukaemia samples. Interestingly, this analysis revealed LIN28B overexpression in 102 childhood leukaemia patients (7.5%), suggesting oncogenic activity for LIN28B in the context of paediatric haematological diseases. As the mode of action of LIN28B during normal and malignant haematopoiesis remains largely unexplored, we subsequently analysed the transcriptional consequences of LIN28B modulation on normal and malignant haematopoietic cells and identified the long non-coding RNA (lncRNA) H19 as the first LIN28B-regulated lncRNA. K562 cells were retrovirally transduced with shRNA GN36578 against LIN28B and a shRNA-miR non-targeting control TRH1103 (both Transomic), selected with puromycin and hybridized on Agilent microarray.
2016-04-07 | E-GEOD-79980 | biostudies-arrayexpress
Project description:In order to examine the consequences of Myc and Lin-28B induction on the transcriptome, P493-6 cells (human EBV-transformed B lymphocytes) were infected with a retrovirus that produces human Lin-28B or empty virus as a control. Gene expression profiles were then monitored in the high and low Myc state using Affymetrix microarrays. Experiment Overall Design: RNA from retrovirally-infected cells with high or low Myc expression was isolated and hybridized to Affymetrix microarrays.
2009-03-14 | E-GEOD-14302 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Refer to individual Series
2013-01-24 | E-GEOD-38825 | biostudies-arrayexpress
Project description:To understand the differentiation program in monocyte/macrophage differentiation, we performed ChIP-seq for IRF8 and H3K4me1 together with gene expression profiling during IRF8-induced monocyte differentiation. Both promoter-proximal and -distal binding of IRF8 associated with induction of the genes especially those related to monocytes/macrophages and immunity. DNA motif analysis for cis-regulatory elements of indirect IRF8 target genes predicted KLF4, essential for Ly6C+ monocyte development, to be a downstream transcription factor regulating the indirect target gene expression. Introduction of KLF4 into an Irf8-/- myeloid progenitor cell line induced a subset of IRF8 target genes and partially induced monocyte/macrophage differentiation. Together, this study revealed the genome-wide behavior of IRF8 and the IRF8-KLF4 axis during monocyte differentiation. Gene expressions in monocyte-like cells differentiated by IRF8 or KLF4 were measured at day 4 after retroviral transductions to myeloid progenitor cell line, Tot2. Two independent experiments were performed.
2013-01-24 | E-GEOD-38810 | biostudies-arrayexpress
Project description:The MYB oncogene is widely expressed in acute leukemias and is important for the continued proliferation of leukemia cells, raising the possibility that MYB may be a therapeutic target. However realization of this potential requires (i) a significant therapeutic window for MYB inhibition, given its essential role in normal hematopoiesis; and (ii) an approach for developing an effective therapeutic. We previously showed that the interaction of Myb with the coactivator CBP/p300 is essential for its transforming activity. Here we use hematopoietic cells from the Booreana mouse strain, which carries a mutation in Myb that prevents interaction with CBP/p300, to examine the requirement for this interaction in myeloid transformation and leukemogenesis. Using this strain and a strain (plt6) carrying a “complementary” mutation in p300, we show that the Myb-p300 interaction is essential for in vitro transformation by the myeloid leukemia oncogenes AML1-ETO, AML1-ETO9a, MLL-ENL, and MLL-AF9. We further show that unlike cells from wild-type (WT) mice, Booreana cells fail to induce leukemia upon transplantation into irradiated recipients following transduction with an AML1-ETO9a retrovirus. These data highlight disruption of the Myb-p300 interaction as a potential therapeutic strategy for AML and suggest that such a strategy would have a useable therapeutic index since Booreana mice, unlike Myb null mice, are viable. Finally we have begun to explore the molecular basis of the these observations by gene expression profiling; this highlighted several genes previously implicated in myeloid leukemogenesis as being differentially expressed between WT and Booreana cells transduced with AML1-ETO9a. Total RNA was obtained from FACS sorted GFP+;c-Kit+ primary bone marrow cells from WT and Booreana mouse strains which had been cultured for 48 hours post-transduction with Control or AML1-ETO9a retroviruses. RNA was extracted from each of 4 samples per group and used to probe Illumina mouse Beadchips array.
2012-12-31 | E-GEOD-34224 | biostudies-arrayexpress
Project description:Chromatins were prepared from myeloid progenitor cell line Tot2 cells transduced with retrovirus for control MSCV or MSCV-IRF8. Chromatin immunoprecipitation (ChIP) was carried out by using anti-IRF8 antibody, anti-PU.1 antibody or anti-histone H3K4me1 antibody. ChIP-Seq peaks were identified using the FindPeaks tool in the HOMER package or SICER with input DNA tags as background distribution. Potential IRF8-direct target genes were identified based on ChIP-Seq and the alteration of expression by IRF8-induction. Examination of 2 transcription factor occupancy and 1 histone modifications in myeloid progenitor cells and monocyte-like cells differetiated by IRF8 expression
2013-01-24 | E-GEOD-38824 | biostudies-arrayexpress
Project description:ASXL1 is the obligate regulatory subunit of a deubiquitinase complex whose catalytic subunit is BAP1. Heterozygous mutations of ASXL1 that result in premature truncations are frequent in myeloid leukemias and Bohring-Opitz syndrome. Here, we demonstrate that truncated ASXL1 proteins confer enhanced activity on the ASXL1-BAP1 complex. Stable expression of truncated, hyperactive ASXL1-BAP1 complexes in a hematopoietic precursor cell line resulted in global erasure of H2AK119Ub, striking depletion of H3K27me3, selective upregulation of a subset of genes whose promoters bore both H2AK119Ub and H3K4me3, and spontaneous differentiation to the mast cell lineage. These outcomes required the catalytic activity of BAP1, indicating these events were downstream consequences of H2AK119Ub erasure. In bone marrow precursors, truncated ASXL1-BAP1 expression cooperated with TET2 loss-of-function to increase differentiation to the myeloid lineage in vivo. We propose that pathological ASXL1 mutations confer gain-of-function on the ASXL-BAP1 complex. ChIP-Seq for H2AK119Ub, H3K4me3, H3K27me3 on EML cells. RNA-Seq on EML cells expressing ASXL1(1-479)+BAP1 and control.
2015-03-11 | E-GEOD-65555 | biostudies-arrayexpress