Ago HITS-CLIP in KSHV-infected primary effusion lymphoma (PEL) cell lines BCBL-1 and BC-3
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE41357 | GEO | 2012/10/05
SECONDARY ACCESSION(S): PRJNA176666
REPOSITORIES: GEO
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Project description:We performed Ago HITS-CLIP to identify targets of viral and human miRNAs in latently KSHV-infected PEL cells Ago HITS-CLIP was performed in two latently infected PEL cell lines, BCBL-1 and BC-3; Argonaute-immunoprecipitation of UV cross-linked Ago-miRNA-mRNA complexes, followed by RNA isolation, library construction, and high-throughput sequencing (Illumina GAxII); we performed 3 biological replicates for each cell line, two technical (sequencing) replicates of BCBL-1 biological replicate 1
2012-10-05 | E-GEOD-41357 | biostudies-arrayexpress
Project description:Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma caused by Kaposi’s sarcoma-associated herpesvirus infection, which is most commonly seen in HIV-positive patients. Induction of HIV reactivation by external stimuli in the presence of highly active anti-retroviral therapy (HAART) has been examined for its efficacy to eradicate latently infected HIV. Similary, lytic activation of viruses from latently infected tumor cells with anti-cancer drugs represents an effective strategy of anti-neoplastic therapy, through the induction of oncolysis by viral replication, stimulation of immune responses to the viral lytic antigens, and intrinsic effects of cancer drugs. Here we examined the combination of PEP005 with epigenetic drugs as a rational therapeutic strategy to target both in AIDS-associated KSHV-mediated malignancies. JQ1, a bromodomain and extra terminal protein (BET) inhibitor, in combination with a FDA-approved drug, PEP005, not only robustly induced KSHV lytic replication, but also inhibited IL-6 and VEGF production from PEL cells. This combination has been proposed for use in reactivation of HIV from latently infected T-cells, and the same combination and dosage inhibited PEL growth in vitro and delayed tumor growth in a PEL xenograft tumor model. Downstream activation of NF-B by PEP005 combined with sequestration of bromodomain-containing protein 4 (BRD4) by JQ1 robustly increased occupancy of RNA polymerase II onto the KSHV genome. RNA-sequencing analysis further revealed cellular targets of PEP005, JQ1, and the synergistic effects of both. We suggest that the combination of PEP005 with JQ1 should be considered as a rational therapeutic approach for HIV-associated PEL.
2017-11-03 | GSE89478 | GEO
Project description:Kaposi’s sarcoma-associated hepesvirus (KSHV) encodes four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3) is expressed in latently infected PEL cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon response. In order to identify cellular genes regulated by vIRF-3, cells from the PEL cell line BC-3 (KSHV positive) were transfected with either siRNAs targeted at vIRF-3 (si463 or si716s) or a negative control siRNA without homology to a known gene (siN, siNs).
2011-01-19 | GSE26661 | GEO
Project description:Kaposi's sarcoma-associated herpesvirus (KSHV) is a human oncogenic virus, which maintains the persistent infection of the host by intermittently reactivating from latently infected cells to produce viral progenies. Here, we performed a comprehensive time course transcriptome analysis during KSHV reactivation in KSHV+ primary effusion B-cell lymphoma cells (PEL). For this we used a recombinant PEL cell line called TRExBCBL1-3xFLAG-RTA. The expression of the N-terminally 3xFLAG-tagged RTA was induced by adding 1 μg/ml doxycycline (Dox) to the medium. Total gene expression changes were identified in TRExBCBL1-3xFLAG-RTA cells at 0, 6, 12, and 24 hours post-induction (hpi).
2019-01-09 | GSE123898 | GEO
Project description:Primary effusion lymphoma (PEL) is a rare B-cell malignancy that originates from B cells latently infected with Kaposi’s sarcoma-associated herpesvirus (KSHV, also known as human herpesvirus-8, HHV8). Our previous data indicated that several exogenous ceramide and dh-ceramide species, such as C18-Cer and dhC16-Cer, also displayed effective anti-cancer activities for KSHV+ PEL in vitro and in vivo. However, the underlying mechanisms for exogenous ceramide “killing” PEL cells still require further investigation, which will be helpful to better understand PEL pathogenesis and identify more potential therapeutic targets. In the current study, we used Illumina microarray to determine the altered gene profile in KSHV+ PEL cell-line, BCBL-1 exposure to dhC16-Cer.
2017-06-10 | GSE90038 | GEO
Project description:Primari effusion lymphoma are (PEL) patient-derived transformed B-cells harboring latent Kaposi's sarcoma-associated herpesvirus (KSHV). The treatment of PEL cells with valproic acid (VA) leads to reactivation of KSHV and viral lytic replication. The aim of this project is to evaluate the effect of KSHV lytic infection on expression of the host transcriptome.
2021-11-08 | GSE179727 | GEO
Project description:KaposiM-bM-^@M-^Ys sarcoma-associated hepesvirus (KSHV) encodes four genes with homology to human interferon regulatory factors (IRFs). One of these IRFs, the viral interferon regulatory factor 3 (vIRF-3) is expressed in latently infected PEL cells and required for their continuous proliferation. Moreover, vIRF-3 is known to be involved in modulation of the type I interferon response. In order to identify cellular genes regulated by vIRF-3, cells from the PEL cell line BC-3 (KSHV positive) were transfected with either siRNAs targeted at vIRF-3 (si463 or si716s) or a negative control siRNA without homology to a known gene (siN, siNs). A total of 4 samples were analyzed. This includes two samples with silencing of vIRF-3 expression via RNA-interference (si463 or si716s) and two samples transfected with a negative-control siRNA (siN, siNs). Expression of vIRF-3 was reduced by approximately 75% as estimated by Western blot analysis.
2011-01-19 | E-GEOD-26661 | biostudies-arrayexpress
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:Primary effusion lymphoma (PEL) is an aggressive subtype of non-Hodgkin lymphoma caused by Kaposi's sarcoma-associated herpesvirus (KSHV) infection. Currently, treatment options for patients with PEL are limited. Oncolytic viruses have been engineered as anticancer agents and have recently shown increased therapeutic promise. Similarly, lytic activation of endogenous viruses from latently infected tumor cells can also be applied as a cancer therapy. In theory, such a therapeutic strategy would induce oncolysis by viral replication, while simultaneously stimulating an immune response to viral lytic cycle antigens. We examined the combination of the FDA-approved drug ingenol-3-angelate (PEP005) with epigenetic drugs as a rational therapeutic approach for KSHV-mediated malignancies. JQ1, a bromodomain and extra terminal (BET) protein inhibitor, in combination with PEP005, not only robustly induced KSHV lytic replication, but also inhibited IL6 production from PEL cells. Using the dosages of these agents that was found to be effective in reactivating HIV (as a means to clear latent virus with highly active antiretroviral therapy), we were able to inhibit PEL growth in vitro and delay tumor growth in a PEL xenograft tumor model. KSHV reactivation was mediated by activation of NF-kB pathway by PEP005, which led to increased occupancy of RNA polymerase II onto the KSHV 33 genome. RNA-sequencing analysis further revealed cellular targets of PEP005, JQ1, and the synergistic effects of both. Thus, combination of PEP005 with a BET inhibitor may be considered as a rational therapeutic approach for the treatment of PEL.
2017-10-24 | GSE103395 | 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 “druggable” 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.
2016-01-05 | GSE70594 | GEO