The EBV latent membrane protein 1 (LMP1) induces cellular microRNA-146a, a modulator of lymphocyte signaling pathways
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE10107 | GEO | 2008/01/09
SECONDARY ACCESSION(S): PRJNA108255
REPOSITORIES: GEO
Similar Datasets
Project description:This SuperSeries is composed of the following subset Series: GSE10057: The Epstein-Barr Virus latent membrane protein 1 (LMP1) induces cellular microRNA146a GSE10105: Alteration of microRNA gene expression by EBV encoded LMP1 oncogene Keywords: SuperSeries Refer to individual Series
2008-01-08 | E-GEOD-10107 | biostudies-arrayexpress
Project description:The Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of nuclear factor kappaB (NF-kappaB). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative reverse transcription-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-kappaB binding sites in the miR-146a promoter and identified a role for an Oct-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a-expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon-responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response.
| S-EPMC2258704 | biostudies-literature
Project description:The Epstein Barr virus (EBV) encoded latent membrane protein-1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of Nuclear Factor-kappaB (NF-kappaB). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis, and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative RT-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-kappaB binding sites in the miR-146a promoter and identified a role for an OCT-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response. Keywords: Analysis of gene expression changes altered by the microRNA, miR-146a EBV positive Burkitt's lymphoma cell line, Akata, was infected with the control retrovirus, pEhyg, or the miR-146a expressing retrovirus, pEhyg-miR-146a. Two infections were carried out for control retrovirus and two infections were carried out with the pEhyg-miR-146a retrovirus. Total RNA was prepared from each of the 4 infections. Control and miR-146a infection set 1 was subjected to dual color array analysis on chip 1. Control and miR-146a infection set 2 was subjected to dual color array analysis on second array of chip 1. Dye swaps of each of these were carried out on two arrays from a second chip (chip 2).
2008-01-03 | E-GEOD-10057 | biostudies-arrayexpress
Project description:The Epstein Barr virus (EBV) encoded latent membrane protein-1 (LMP1) is a functional homologue of the tumor necrosis factor receptor family and contributes substantially to the oncogenic potential of EBV through activation of Nuclear Factor-kappaB (NF-kappaB). MicroRNAs (miRNAs) are a class of small RNA molecules that are involved in the regulation of cellular processes such as growth, development, and apoptosis, and have recently been linked to cancer phenotypes. Through miRNA microarray analysis, we demonstrate that LMP1 dysregulates the expression of several cellular miRNAs, including the most highly regulated of these, miR-146a. Quantitative RT-PCR analysis confirmed induced expression of miR-146a by LMP1. Analysis of miR-146a expression in EBV latency type III and type I cell lines revealed substantial expression of miR-146a in type III (which express LMP1) but not in type I cell lines. Reporter studies demonstrated that LMP1 induces miR-146a predominantly through two NF-kappaB binding sites in the miR-146a promoter and identified a role for an OCT-1 site in conferring basal and induced expression. Array analysis of cellular mRNAs expressed in Akata cells transduced with an miR-146a expressing retrovirus identified genes that are directly or indirectly regulated by miR-146a, including a group of interferon responsive genes that are inhibited by miR-146a. Since miR-146a is known to be induced by agents that activate the interferon response pathway (including LMP1), these results suggest that miR-146a functions in a negative feedback loop to modulate the intensity and/or duration of the interferon response. Keywords: Analysis of gene expression changes altered by the microRNA, miR-146a
2008-01-04 | GSE10057 | GEO
Project description:The Epstein-Barr virus (EBV) oncoprotein latent membrane protein 1 (LMP1) is thought to act as the major transforming protein in various cell types, by rerouting the tumor necrosis factor receptor family signaling pathway. Despite this implication in EBV-associated transformation of cells, LMP1 toxicity is a well-known but poorly studied feature, perhaps because it contradicts its role in transformation. We show that LMP1 physiological levels are very heterogeneous and that the highest levels of LMP1 correlate with Fas overexpression and spontaneous apoptosis in lymphoblastoid cell lines (LCLs). To understand the cytotoxic effect of LMP1 in LCLs, we cloned wild-type LMP1 into a doxycycline double-inducible episomal vector pRT-1, with a truncated version of NGFR as a surrogate marker of inducibility. We found that LMP1 overexpression induced apoptosis in LCL B cells, as shown by annexin V labeling, sub-G(1) peak, and poly(ADP ribose) polymerase cleavage. Knocking down Fas expression by small interfering RNA abolished LMP1-induced apoptosis. The absence of detectable levels of Fas ligand mRNA suggested a ligand-independent activation of Fas. LMP1 induced Fas overexpression with its relocalization in lipid raft microdomains of the membrane. Fas immunoprecipitation detected FADD (Fas-associated death domain protein) and caspase 8, suggesting a Fas-dependent formation of the death-inducing signaling complex. Caspases 8, 9, 3, and 7 were activated by LMP1. Caspase 8 activation was associated with BID cleavage and truncated-BID mitochondrial relocalization, consistent with type II apoptosis. Therefore, our results are in agreement with a model where LMP1-dependent NF-kappaB activation induces Fas overexpression and autoactivation that could overwhelm the antiapoptotic effect of NF-kappaB, revealing an ambivalent function of LMP1 in cell survival and programmed cell death.
| S-EPMC2447067 | biostudies-literature
Project description:Extracellular vesicles (EV) mediate intercellular communication events and alterations in normal vesicle content contribute to function and disease initiation or progression. The ability to package a variety of cargo and transmit molecular information between cells renders EVs important mediators of cell to cell crosstalk. Latent membrane protein 1 (LMP1) is a chief viral oncoprotein expressed in most Epstein-Barr virus (EBV)-associated cancers and is released from cells at high levels in EVs. LMP1 containing EVs have been demonstrated to promote cell growth, migration, differentiation, and regulate immune cell function. Despite these significant changes in recipient cells induced by LMP1 modified EVs, the mechanism how this viral oncogene modulates the recipient cells towards these phenotypes is not well understood. We hypothesize that LMP1 alters EV content and following uptake of the LMP1-modified EVs by the recipient cells results in the activation of cell signaling pathways and increased gene expression which modulates the biological properties of recipient cell towards a new phenotype. Our results show that LMP1 expression alters the EV protein and microRNA content packaged into EVs.
2020-11-03 | PXD021914 | Pride
Project description:An Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP1) is a principal oncogene that plays a pivotal role in EBV-associated malignant tumors including nasopharyngeal cancer (NPC). Recent genomic landscape studies revealed that NPC also contained many genomic mutations, suggesting the role of LMP1 as a driver gene for the induction of these genomic mutations. Nonetheless, its exact mechanism has not been investigated. In this study, we report that LMP1 alters the expression profile of APOBEC3s(A3s), host deaminases that introduce consecutive C-to-U mutations (hypermutation). In vitro, LMP1 induces APOBEC3B (A3B) and 3F(A3F), in a nasopharyngeal cell line, AdAH. Overexpression of LMP1, A3B, or A3F induces mtDNA hypermutation, which is also detectable from NPC specimens. Expression of LMP1 and A3B in NPC was correlated with neck metastasis. These results provide evidence as to which LMP1 induces A3s and mtDNA hypermutation, and how LMP1 facilitates metastasis is also discussed.
| S-EPMC7571841 | biostudies-literature
Project description:Expression of mRNAs in an EBV-positive B-cell strain, 28-2. 28-2 are infected with a derivative of the B-958 strain of EBV, which expresses eGFP constitutively and LMP1 fused to mRFP from its native promoter. Single cells were sorted by flow cytometry for their levels of LMP1-mRFP (5% expressing the lowest levels of LMP1-mRFP or 5% expressing the highest levels of LMP1-mRFP) Two-condition experiment: Low v. High LMP1-mRFP expression. Biological replicates: 3 Low LMP1-mRFP, 3 High LMP1-mRFP. Samples were normalized to the expression of mRNAs in a pool of unsorted 28-2 cells.
2012-02-01 | E-GEOD-33673 | biostudies-arrayexpress
Project description:The Epstein-Barr virus (EBV) is a ubiquitous γ herpesvirus strongly associated with nasopharyngeal carcinomas, and the viral oncogenicity in part relies on cellular effects of the viral latent membrane protein 1 (LMP1). It was previously described that EBV strains B95.8 and M81 differ in cell tropism and the activation of the lytic cycle. Nonetheless, it is unknown whether LMP1 from these strains have different effects when expressed in nasopharyngeal cells. Thus, herein we evaluated the effects of EBV LMP1 derived from viral strains B95.8 and M81 and expressed in immortalized nasopharyngeal cells NP69SV40T in the regulation of 91 selected cellular miRNAs. We found that cells expressing either LMP1 behave similarly in terms of NF-kB activation and cell migration. Nonetheless, the miRs 100-5p, 192-5p, and 574-3p were expressed at higher levels in cells expressing LMP1 B95.8 compared to M81. Additionally, results generated by in silico pathway enrichment analysis indicated that LMP1 M81 distinctly regulate genes involved in cell cycle (i.e., RB1), mRNA processing (i.e., NUP50), and mitochondrial biogenesis (i.e., ATF2). In conclusion, LMP1 M81 was found to distinctively regulate miRs 100-5p, 192-5p, and 574-3p, and the in silico analysis provided valuable clues to dissect the molecular effects of EBV LMP1 expressed in nasopharyngeal cells.
| S-EPMC8871543 | biostudies-literature
Project description:Expression of mRNAs in an EBV-positive B-cell strain, 28-2. 28-2 are infected with a derivative of the B-958 strain of EBV, which expresses eGFP constitutively and LMP1 fused to mRFP from its native promoter. Single cells were sorted by flow cytometry for their levels of LMP1-mRFP (5% expressing the lowest levels of LMP1-mRFP or 5% expressing the highest levels of LMP1-mRFP)
2012-02-01 | GSE33673 | GEO