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SOX11-positive and SOX11-knockdown xenograft derived tumor Gene Expression Profilings

ABSTRACT: The neural transcription factor SOX11 is overexpressed in aggressive lymphoid neoplasms mainly in mantle cell lymphoma (MCL). We have recently demonstrated SOX11 tumorigenic potential in vivo by showing a significant reduction on tumor growth of SOX11-knockdown MCL cells in xenograft experiments, confirming the clinical observations that SOX11 may play an important role in the aggressive behavior of MCL (Vegliante et al., 2013). However, the specific mechanisms regulated by SOX11 that promote the oncogenic and rapid tumor growth of aggressive MCL still remain to be elucidated. To further characterize the potential oncogenic mechanisms regulated by SOX11 in MCL, we have analyzed the GEP derived from the xenograft SOX11-positive and knockdown xenograft derived tumors. Differential gene expression between SOX11-positive Z138 and SOX11-negative Z138 MCL cell lines xenotransplanted in SCID mices derived tumors.

ORGANISM(S): Homo sapiens

PROVIDER: GSE52892 | GEO | 2014/11/04

SECONDARY ACCESSION(S): PRJNA230401

REPOSITORIES: GEO

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SOX11-positive and SOX11-knockdown xenograft derived tumor Gene Expression Profilings

Project description:The neural transcription factor SOX11 is overexpressed in aggressive lymphoid neoplasms mainly in mantle cell lymphoma (MCL). We have recently demonstrated SOX11 tumorigenic potential in vivo by showing a significant reduction on tumor growth of SOX11-knockdown MCL cells in xenograft experiments, confirming the clinical observations that SOX11 may play an important role in the aggressive behavior of MCL (Vegliante et al., 2013). However, the specific mechanisms regulated by SOX11 that promote the oncogenic and rapid tumor growth of aggressive MCL still remain to be elucidated. To further characterize the potential oncogenic mechanisms regulated by SOX11 in MCL, we have analyzed the GEP derived from the xenograft SOX11-positive and knockdown xenograft derived tumors. Differential gene expression between SOX11-positive Z138 and SOX11-negative Z138 MCL cell lines xenotransplanted in SCID mices derived tumors. To determine the transcriptional programs regulated by SOX11 we first generated a MCL cellular model with reduced SOX11 protein levels by infecting MCL cell lines with lentiviral particles carrying shRNA plasmids specifically targeting SOX11 (shSOX11.1 and shSOX11.3). Next, CB17-severe combined immunodeficient (CB17-SCID) mice (Charles River Laboratory, Wilmington, MA) were subcutaneously inoculated into their lower dorsum with Z138 shSOX11.1, shSOX11.3, shControl in Matrigel basement membrane matrix and compared the GEP of SOX11-positive and SOX11-negative MCL xenotransplant derived tumors using the Affymetrix U133+2.0 microarrays.

2014-11-04 | E-GEOD-52892 | biostudies-arrayexpress

SOX11 Gene Expression Profiling

2013-04-04 | GSE34763 | GEO

SOX11 Gene Expression Profiling

Project description:The neural transcription factor SOX11 is overexpressed in aggressive lymphoid neoplasms mainly in mantle cell lymphoma (MCL), but its functional role in malignant B-cells is unknown. To identify target genes transcriptionally regulated by SOX11 in malignant lymphoid cells, we have used Gene Expression Profiling (GEP) after SOX11 silencing in MCL cell lines. Differential gene expression between Z138-shSOX11 and Z138-shControl MCL cell lines. To determine the transcriptional programs regulated by SOX11, we first generated an MCL cellular model with reduced SOX11 protein levels by infecting MCL cell lines with lentiviral particles carrying shRNA plasmids specifically targeting SOX11 (shSOX11.1 and shSOX11.3). Next, we compared the GEP of shSOX11 and shControl Z138 stable transduced clones using the Affymetrix U133+2.0 microarrays.

2013-04-04 | E-GEOD-34763 | biostudies-arrayexpress

Chip-chip from Z138 MCL cell line with SOX11 antibody

Project description:To determine the role of SOX11 in aggressive lymphoid neoplasm, we first investigated direct target genes of this transcription factor using chromatin immunoprecipitation and DNA microarrays (ChIP-chip) in MCL cell lines. Analysis of the exact location of SOX11 binding elements showed that SOX11 interacts with DNA predominantly in the enhancer regions (in 40% of the enriched regions) and intron segments (in 33% of the enriched regions), suggesting that in these genes SOX11 may interact with the general transcriptional machinery and transcriptional co-regulators.

2015-01-01 | GSE35021 | GEO

The genes regulated by SOX11 in mantle cell lymphoma

Project description:The genes regulated by SOX11 in MCL was investigated in MCL cell line Granta 519 by siRNA knock down system. Cells were transfected using the LONZA electroporation system. Results represent cells harvested after 20 hours. Details of the experiment is published in PMID 21124928. Gene expression profiles (Human Gene 1.0 ST) of mantle cell lymphoma (MCL) cell line Granta 519 treated with SOX11 siRNA. Data analyses were performed using the Affymetrix Expression Console (v. 1.1)

2010-11-29 | E-GEOD-25621 | biostudies-arrayexpress

High resolution ChIP sequencing reveals novel bindings targets and prognostic role for SOX11 in Mantle cell lymphoma (RNA-Seq)

Project description:SOX11 (Sex determining region Y-box 11) expression is specific for MCL as compared to other Non-HodgkinM-bM-^@M-^Ys lymphomas. However, the function and direct binding targets of SOX11 in MCL are largely unknown. We used high-resolution ChIP-Seq to identify the direct target genes of SOX11 in a genome-wide, unbiased manner and elucidate its functional significance. Pathway analysis identified WNT, PKA and TGF-beta signaling pathways as significantly enriched by SOX11 target genes. qCHIP confirmed that SOX11 directly binds to individual genes in these pathways in both MCL cell lines and patients. Interrogation of an eighty-two patientM-BM- gene-expression dataset demonstrated that SOX11 mRNA expression was inversely proportional to Ki-67, a marker of cell proliferation. Functional studies using RNA interference demonstrate that SOX11 directly regulates WNT signaling and modulates chemotherapy sensitivity to cytarabine in MCL. We analyzed SOX11 expression in three independent well-annotated tissue microarrays from the University of Wisconsin (UW), Karolina Institute and British Columbia Cancer Agency (BCCA). Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy incorporating cytarabine. Transcriptional regulation of WNT and other biological pathways affects by SOX11 target genes may help explain the impact of SOX11 expression on patient outcomes. RNA-seq experiments studying SOX11-mediated regulation of gene transcription by examining genes differentially expressed following SOX11 depletion in 3 MCL cell lines, Granta-519, Z138 and JEKO-1

2014-08-07 | E-GEOD-52148 | biostudies-arrayexpress

High resolution ChIP sequencing reveals novel bindings targets and prognostic role for SOX11 in Mantle cell lymphoma (RNA-Seq)

Project description:SOX11 (Sex determining region Y-box 11) expression is specific for MCL as compared to other Non-Hodgkin’s lymphomas. However, the function and direct binding targets of SOX11 in MCL are largely unknown. We used high-resolution ChIP-Seq to identify the direct target genes of SOX11 in a genome-wide, unbiased manner and elucidate its functional significance. Pathway analysis identified WNT, PKA and TGF-beta signaling pathways as significantly enriched by SOX11 target genes. qCHIP confirmed that SOX11 directly binds to individual genes in these pathways in both MCL cell lines and patients. Interrogation of an eighty-two patient gene-expression dataset demonstrated that SOX11 mRNA expression was inversely proportional to Ki-67, a marker of cell proliferation. Functional studies using RNA interference demonstrate that SOX11 directly regulates WNT signaling and modulates chemotherapy sensitivity to cytarabine in MCL. We analyzed SOX11 expression in three independent well-annotated tissue microarrays from the University of Wisconsin (UW), Karolina Institute and British Columbia Cancer Agency (BCCA). Our findings suggest that high SOX11 expression is associated with improved survival in a subset of MCL patients, particularly those treated with intensive chemotherapy incorporating cytarabine. Transcriptional regulation of WNT and other biological pathways affects by SOX11 target genes may help explain the impact of SOX11 expression on patient outcomes.

2014-08-07 | GSE52148 | GEO

High resolution ChIP sequencing reveals novel bindings targets and prognostic role for SOX11 in Mantle cell lymphoma (ChIP-Seq)

2014-08-07 | GSE52146 | GEO

Expression profiles of SOX11-positive and SOX11-negative Mantle Cell Lymphoma (MCL) primary samples from lymph node and reactive lymph nodes (RLN).

Project description:Gene expression profiles were obtained via Nanostring nCounter Expression Assay (PanCancer Immune Profiling Panel, Nanostring Technologies, Hamburg, Germany). We aimed to obtain the differential immune gene expression comparing the lymph node microenvironment of SOX11-positive and SOX11-negative MCL primary samples and non-neoplastic nodal samples (RLN).

2021-12-01 | GSE141539 | GEO

The genes regulated by SOX11 in mantle cell lymphoma

2010-11-29 | GSE25621 | GEO

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