Browse
Submit Data
Databases
API
Help

Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

13 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

A novel non-coding RNA within WHSC1 is over-expressed in t(4;14)-positive multiple myeloma and other cancers

ABSTRACT: We designed oligonucleotide tiling arrays spanning the t(4;14) breakpoint region on chromosome 4 to identify additional oncogenic RNAs in an unbiased fashion. Four (4) multiple myeloma bone marrow samples with t(4;14) and twelve (12) MM BM samples without t(4;14) were analyzed. Furthermore, seven (7) bladder (1 normal, 6 malignant), eight (8) colon (1 normal, 7 malignant) and eight (8) esophagus (2 normal, 6 maligant) tissue samples were analyzed. Finally, five (5) multiple myeloma cell line samples with t(4;14) - three (3) of LP-1 and two (2) of H929 - and three (3) MM cell line samples and three (3) non-MM cell line samples without t(4;14) - three (3) of U266 and three (3) of Hela - were analyzed.

ORGANISM(S): Homo sapiens

SUBMITTER: Mack Su

PROVIDER: E-GEOD-36685 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

HDAC and aminopeptidase inhibitor treatment of myeloma cells

Project description:H929 human myeloma cells were exposed to aminopeptidase inhibitor (CHR-2797), HDAC inhibitor (CHR-3996), or a combinaion of the two agents, for 24 hours. Following this treatment RNA was extracted and microarrays used to determine gene expression changes. Myeloma cells were exposed to chemotherapeutic agent for 24 hours.

2014-01-24 | E-GEOD-20405 | biostudies-arrayexpress

NSD2 interacts with SMARCA2 and regulates expression of oncogenes CCND1 and PRL3 in t(4;14) multiple myeloma

Project description:Recurrent chromosomal translocations are central to the pathogenesis of multiple myeloma (MM), with t(4;14) translocation being the second-most common and associated with poor prognosis. The nuclear receptor-binding SET domain 2 (NSD2) is overexpressed as a result of the translocation and has been suggested to be the primary oncogenic factor in t(4;14) MM. However, the detailed oncogenic mechanism of NSD2 in MM is still not completely understood. To address the relevant pathways downstream of NSD2 that contributes to myelomagenesis, SILAC-based mass-spectrometry analysis was used to determine NSD2-interacting proteins. We identified 74 proteins and in silico analysis showed that one of them, SMARCA2, interacts with NSD2. Comparison of SMARCA2 expression across MM cell lines with different translocation statuses showed that SMARCA2 was highly expressed in t(4;14) MM cells but not in non-t(4;14) MM cells. SMARCA2 knockdown in t(4;14) MM cells showed reduced cell growth and capacity to form colonies. We further investigated how NSD2 and SMARCA2 regulate the expressions of key myeloma genes, such as PRL3 and CCND1. This study reveals a spectrum of NSD2-interacting proteins involved in different biological pathways, indicating the importance of NSD2 in t(4;14) MM. The interaction between NSD2 and SMARCA2 in regulating the expression of CCND1 and PRL3 suggests the potential of SMARCA2 as a novel therapeutic target for t(4;14) MM.

2021-07-15 | GSE140860 | GEO

MMSET alters EZH2 Binding in Myeloma Cells

Project description:We investigated EZH2 binding in the presence and absence of MMSET protein. MMSET overexpression in t(4;14)+ myeloma leads to global loss of H3K27 methylation and redistribution of EZH2 binding throughout the genome ChIP-seq for EZH2 in two cell types

2014-09-01 | E-GEOD-57632 | biostudies-arrayexpress

MMSET regulates transcription factors critical for survival of t(4;14) myeloma myeloma cells

Project description:Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. The multiple myeloma SET domain (MMSET), identified by its fusion to the IgH locus in t(4;14) MM, is universally overexpressed and has been suggested to play an important role in tumorigenicity in t(4;14) MM. In order to identify downstream functional targets of MMSET, we knocked down MMSET expression with shRNAs in KMS11, a t(4;14) MM cell line, and identified differentially expressed genes by gene expression microarray analysis.

2014-07-16 | GSE59424 | GEO

MMSET I acts as an oncoprotein and regulates GLO1 expression in t(4;14) multiple myeloma cells

Project description:Multiple myeloma (MM) is characterized by recurrent chromosomal translocations. The translocation t(4;14)(p16;q32) is one of the most common translocation in MMs, affecting 15% of patients, and is associated with very poor prognosis. The histone methyltransferase (HMTase) MMSET is universally overexpressed in t(4;14) MM as a result of the t(4;14) translocation. MMSET is capable of producing 3 major isoforms, the full length MMSET II, short isoforms REIIBP and MMSET I. MMSET II has been suggested to play an important tumorigenic role in t(4;14) MM, but little is yet known about whether and how the MMSET short isoforms contribute to MM tumorigenesis. The aim of this study is to characterize MMSET I roles and determine its downstream targets in t(4;14) MM. In t(4;14) MM cells MMSET I knockdown with shRNAs induced cell apoptosis, reduced colony formation and inhibited tumorigenicity in vivo. We also found MMSET I knockdown decreased GLO1 expression, and ectopic MMSET I increased GLO1 expression, suggesting that MMSET I is an upstream regulator of GLO1. Further analysis indicated that MMSET I bound to GLO1 promoter region and depended on its C-terminus to regulate GLO1 expression. Our preliminary data suggested that MMSET I is an oncoprotein and could regulate GLO1 expression in t(4;14) multiple myeloma cells.

2019-01-01 | GSE98433 | GEO

MMSET Induces Global and Focal Changes in Histone Methylation in Myeloma Cells

Project description:We investigated genome wide distribution of H3K36me2, H3K36me3 and H3K27me3 in the presence and absence of MMSET protein. MMSET overexpression in t(4;14)+ myeloma leads to global loss redistribution of H3K36me2 and genome-wide loss of H3K27 methylation. Despite the gloal decrease in H3K27me3, specific regions of the genome show enhanced H3K27me3 enrichment through increased recruitment of EZH2 methyltransferase ChIP-seq for H3K36me2, H3K36me3 and H3K27me3 in two cell types

2014-09-01 | E-GEOD-57977 | biostudies-arrayexpress

Changes in gene expression in BAZ1B knockout and heterozygous targeted clones

Project description:Williams syndrome transcription factor (WSTF) is a multifaceted protein that is involved in several nuclear processes, including replication, transcription, and the DNA damage response. WSTF participates in a chromatin-remodeling complex with the ISWI ATPase, SNF2H, and is thought to contribute to the maintenance of heterochromatin, including at the human inactive X chromosome (Xi). WSTF is encoded by BAZ1B, and is one of twenty-eight genes that are hemizygously deleted in the genetic disorder Williams-Beuren syndrome (WBS). To explore the function of WSTF, we performed zinc finger nuclease-assisted targeting of the BAZ1B gene and isolated several independent knockout clones in human cells. Our results show that, while heterochromatin at the Xi is unaltered, new inappropriate areas of heterochromatin spontaneously form and resolve throughout the nucleus. In three independent mutants, the expression of a large number of genes were impacted, both up and down, by WSTF loss. In addition, we found that cells lacking WSTF responded appropriately to vitamin D treatment, a process we expected to be disrupted. Given the inappropriate appearance of regions of heterochromatin in BAZ1B knockout cells, it is evident that WSTF performs a critical role in maintaining chromatin and transcriptional states. Clearly, further exploration is necessary to fully understand the role of WSTF in maintenance of the epigenome and how WSTF haploinsufficiency contributes to the wide array of symptoms exhibited in WBS patients. Samples include three replicate miroarray hybridizations of the parental cells (hTERT-RPE1), three replicates from three independent knock-out clones (D5, F3 and M1), and one set of replicates for a heterozygous mutant clone (A6).

2014-05-21 | E-GEOD-47390 | biostudies-arrayexpress

Transcription profiling of mouse glioma cell line grown in two types of media to investigate cell de-differentiation

Project description:Comparison of gene expression profiles of the GL261 cell line (a murine glioma model) grown in duplicate in two different types of media. AC samples where grown in DMEM supplemented by 20% FBS, 5 U/ml pen/strep and 4 mM L-glutamine. NS samples were grown in DMEM/F12 (50/50) supplemented with 2 U/ml pen/strep, 1 ug/ml fungizone, 1x B27, 20 ng/ml bFGF, 20 ng/ml EGF, 20 ng/ml LIF and 5 ug/ml heparin. We have reason to believe the NS media enhances cell de-differentiation.

2006-12-31 | E-MEXP-718 | biostudies-arrayexpress

NF-kB activation confers a prolonged event-free-survival in newly diagnosed myeloma patients harboring t(4;14) treated with bortezomib.

Project description:NF-kB pathway activation is the hallmark of hematological malignancies. In multiple myeloma (MM), a large variety of genomic alterations leading to either inactivation of repressor such as TRAF3, CYLD or cIAP1/2 or amplification of activators such as CD40 or NIK collectively contribute to frequently deregulate NF-kB signaling. In order to evaluate the prognostic impact of NF-kB mutations in MM, we performed a comprehensive analysis of a panel of newly diagnosed patients with cIAP1/2 biallelic deletion. We found that all patients have dysregulated NF-kB pathway and the majority of them presented t(4;14). Then we analyzed clinical outcome of 37 MM at presentation with t(4;14) and treated with bortezomib according to their NF-kB status. We showed that increase of NF-kB activity confers prolonged event-free survival. Altogether, our data suggest that NF-kB activation resulting from NF-kB mutations (ie cIAP1/2 deletion) or other mechanisms improves outcome of t(4;14)-positive MM treated with bortezomib.

2015-09-15 | GSE31272 | GEO

Effects of MMSET on gene expression in multiple myeloma

Project description:The MMSET (Multiple Myeloma SET domain) protein is overexpressed in multiple myeloma patients with the translocation t(4;14). Although studies have shown the involvement of MMSET/WHSC1 in development, its mode of action in the pathogenesis of multiple myeloma (MM) is largely unknown. We found that MMSET is a major regulator of chromatin structure and transcription in t(4;14) MM cells. High levels of MMSET correlate with an increase in lysine 36 methylation of histone H3 and a decrease in lysine 27 methylation across the genome, leading to a more open structural state of the chromatin. Loss of MMSET expression alters adhesion properties, suppresses growth and induces apoptosis in MM cells. Consequently, genes affected by high levels of MMSET are implicated in the p53 pathway, cell cycle regulation and integrin signaling. Regulation of many of these genes required functional histone methyl-transferase (HMT) activity of MMSET. These results implicate MMSET as a major epigenetic regulator in t(4;14)+ MM.

2010-10-20 | GSE24746 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data