Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA381391 | ENA |
REPOSITORIES: ENA
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Project description:Primary effusion lymphoma (PEL), which is an aggressive lymphoma associated with Kaposi sarcoma-associated herpesvirus/human herpes virus-8 (KSHV/HHV-8), is refractory to standard chemotherapy, and exhibits a poor prognosis. Although PU.1 is down-regulated in PEL among B-cell transcription factors, the potential role of its reduction remains to be elucidated. In this investigation, we analyzed the DNA methylation of PU.1 cis-regulatory elements in PEL and the effect of restoring PU.1 on PEL cells. The expression of PU.1 mRNA was down-regulated in PEL cells. The promoter and enhancer regions of the PU.1 gene were highly methylated. The restoration of PU.1 inhibited cell growth and induced apoptosis in PEL cells. A microarray analysis revealed that interferon-stimulated genes (ISGs) including pro-apoptotic ISGs were strongly increased in BCBL-1 cells after the induction of PU.1. The up-regulation of PU.1 induced the transactivation of pro-apoptotic ISG promoters, such as the XAF1, OAS1, and TRAIL promoters, in reporter assays. Mutations at the PU.1 binding sites suppressed its transactivation. We confirmed the binding of PU.1 to the XAF1, OAS1, and TRAIL promoters in a chromatin immunoprecipitation assay. PU.1 suppressed ORF57 activation by inducing IRF7. The reinduction of PU.1 reduced formation of ascites and lymphoma cell infiltration of distant organs in PEL xenograft model mice. These results suggest that PU.1 plays a role in tumor suppression in PEL and its down-regulation is associated with PEL development. Up-regulation of PU.1 with demethylation agents may be a novel therapeutic strategy for PEL.
2019-02-28 | GSE97318 | GEO
Project description:c-MET inhibitor inducing KSHV+ primary effusion lymphoma apoptosis
| PRJNA289124 | ENA
Project description:PU.1 is an Ets family transcription factor that is essential for the differentiation of both myeloid and lymphoid cells. PU.1 is down-regulated in classical Hodgkin lymphoma cells via methylation of the PU.1 promoter. To evaluate whether down-regulation of PU.1 is essential for the growth of cHL cells, we generated L428 derived cell lines conditionally express PU.1 by tet-off system (designated L428tetPU.1). Conditonally expressed PU.1 by tetracycline removal induced complete growth arrest and apoptosis in L428 cells. To elucidate the mechanisms underlying cell cycle arrest and apoptosis induced by PU.1, we compared gene expression profiles of L428tetPU.1 cells 0, 1 and 3 days after PU.1 induction, by DNA microarray. We extracted total RNA from L428tetPU.1 cells 0, 1 and 3 days after PU.1 induction by tetracycline removal. We compared gene expression profiles of KL428tetPU.1 cells 0, 1 and 3 days after PU.1 induction using DNA microarray analysis. 4 independent experiments were performed with each RNA samples.
2012-11-22 | E-GEOD-42437 | biostudies-arrayexpress
Project description:PU.1 is an Ets family transcription factor that is essential for the differentiation of both myeloid and lymphoid cells. PU.1 is down-regulated in classical Hodgkin lymphoma cells via methylation of the PU.1 promoter. To evaluate whether down-regulation of PU.1 is essential for the growth of cHL cells, we generated KM-H2 derived cell lines conditionally express PU.1 by tet-off system (designated KM-H2tetPU.1). Conditonally expressed PU.1 by tetracycline removal induced complete growth arrest and apoptosis in KM-H2 cells. To elucidate the mechanisms underlying cell cycle arrest and apoptosis induced by PU.1, we compared gene expression profiles of KM-H2tetPU.1 cells 0, 1 and 3 days after PU.1 induction, by DNA microarray. We extracted total RNA from KM-H2tetPU.1 cells 0, 1 and 3 days after PU.1 induction by tetracycline removal. We compared gene expression profiles of KM-H2tetPU.1 cells 0, 1 and 3 days after PU.1 induction using DNA microarray analysis. 4 independent experiments were performed with each RNA samples.
2012-11-22 | E-GEOD-42440 | biostudies-arrayexpress
Project description:PU.1 is an Ets family transcription factor that is essential for the differentiation of both myeloid and lymphoid cells. PU.1 is down-regulated in classical Hodgkin lymphoma cells via methylation of the PU.1 promoter. To evaluate whether down-regulation of PU.1 is essential for the growth of cHL cells, we generated KM-H2 derived cell lines conditionally express PU.1 by tet-off system (designated KM-H2tetPU.1). Conditonally expressed PU.1 by tetracycline removal induced complete growth arrest and apoptosis in KM-H2 cells. To elucidate the mechanisms underlying cell cycle arrest and apoptosis induced by PU.1, we compared gene expression profiles of KM-H2tetPU.1 cells 0, 1 and 3 days after PU.1 induction, by DNA microarray.
2012-11-22 | GSE42440 | GEO
Project description:PU.1 is an Ets family transcription factor that is essential for the differentiation of both myeloid and lymphoid cells. PU.1 is down-regulated in classical Hodgkin lymphoma cells via methylation of the PU.1 promoter. To evaluate whether down-regulation of PU.1 is essential for the growth of cHL cells, we generated L428 derived cell lines conditionally express PU.1 by tet-off system (designated L428tetPU.1). Conditonally expressed PU.1 by tetracycline removal induced complete growth arrest and apoptosis in L428 cells. To elucidate the mechanisms underlying cell cycle arrest and apoptosis induced by PU.1, we compared gene expression profiles of L428tetPU.1 cells 0, 1 and 3 days after PU.1 induction, by DNA microarray.
2012-11-22 | GSE42437 | GEO
Project description:Downregulation of the hematopoietic transcription factor PU.1 in PU.1 low acute myeloid leukemia cells (AML) by novel heterocyclic diamidines or PU.1 inhibitors leads to decrease cell proliferation and apoptosis, representing a new therapeutic strategy for AML treatment. These inhibitors induces decreased PU.1 binding on its target sites, as well as deregulation in PU.1 canonical target genes We used microarray to identify the pathways deregulated after drug treatment.
2017-12-07 | GSE77651 | GEO
Project description:KSHV is a principal causative agent of primary effusion lymphoma (PEL). Despite this knowledge about the close relationship between HGF/c-MET network and solid tumors development, the role of HGF/c-MET in KSHV-related malignancies remains mostly unclear. We report that HGF/c-MET pathway is highly active within KSHV+ PEL cells and plays important role in tumor cell survival/growth. Targeting HGF/c-MET by a selective inhibitor, PF-2341066, significantly induces PEL apoptosis through a complex of underlying mechanisms, including cell-cycle arrest and DNA damage. By using microarray analysis, we have identified the global gene profile controlled by HGF/c-MET pathway within KSHV+ PEL cell-lines and several novel âdruggableâ candidates closely related to cancer cell survival/growth. Finally, we found that targeting HGF/c-MET pathway by PF-2341066 effectively prevents PEL tumor expansion and/or reduce established lymphoma progression in vivo. PEL cells were treated with vehicle control or c-MET inhibitor PF-2341066 (0.8 µM) for 24 h, and the gene expression signature was compared to respective vehicle controls
2016-01-05 | E-GEOD-70594 | biostudies-arrayexpress
Project description:Kaposiâs sarcoma-associated herpesvirus (KSHV) is the etiological agent of primary effusion lymphoma (PEL), a rapidly progressing malignancy mostly arising in HIV-infected patients. Even under conventional chemotherapy, PEL continues to portend nearly 100% mortality within several months, which urgently requires novel therapeutic strategies. We have previously demonstrated that targeting xCT, an amino acid transporter for cystine/glutamate exchange, induces significant PEL cell apoptosis through regulation of multiple host and viral factors. More importantly, one of xCT selective inhibitors, Sulfasalazine (SASP), effectively prevents PEL tumor progression in an immune-deficient xenograft model. In the current study, we use Illumina microarray to explore the genomic gene profile altered by SASP treatment within 3 KSHV+ PEL cell-lines, and discover that many genes involved in oxidative stress/antioxidant defense system, apoptosis/anti-apoptosis/cell death, and cellular response to unfolded proteins/topologically incorrect proteins are potentially regulated by xCT. We further functionally validate 2 downstream candidates, OSGIN1 (Oxidative stress-induced growth inhibitor 1) and XRCC5 (X-ray repair cross-complementing protein 5), their relationship with PEL cell survival/proliferation and chemoresistance, respectively. Together, our data indicate that targeting these xCT-regulated novel downstream genes may help devise promising therapeutic strategies against PEL and/or other AIDS-related lymphoma. 3 KSHV PEL cell lines were treated with xCT selective inhibitor Sulfasalazine (SASP) and the gene expression signature was compared to that of untreated cells
2015-11-23 | E-GEOD-65418 | biostudies-arrayexpress
Project description:The Kaposi's sarcoma-associated herpesviruses causes several cancers including Kaposi's sarcoma and primary effusion lymphoma (PEL). Our work reveals that the cellular transcription factors interferon regulatory factor 4 (IRF4) and basic leucine zipper ATF-like transcription factor (BATF), as well as the viral interferon regulatory factor 3 (vIRF3) are critical oncogenic dependencies specific to PEL cell lines. To understand the functions of these transcription factors, we performed ChIP-Seq on these proteins in BC-3 PEL cell line. Our results reveal that these oncogenic factors may cooperate to regulate the expression of the same mRNAs.
2020-08-13 | GSE132777 | GEO