Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas

Navari, Mohsen; Etebari, Maryam; Ibrahimi, Mostafa; Leoncini, Lorenzo; Piccaluga, Pier Paolo

doi:10.3390/ijms19041168

Cited by 33 publications

(28 citation statements)

References 121 publications

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“…77 Some studies have focused on the role of EBVencoded miRNAs and NKTCL pathogenesis. 78,79 One of these studies showed that an EBVexpressed miRNA (i.e. BART9 miRNA) is overexpressed in two NKTCL cell lines, and it promotes cellular growth by upregulating LMP1, an oncogene encoded by EBV.…”

Section: Noncoding Rnas In Nktcl Pathogenesismentioning

confidence: 99%

Epigenetic aberrations in natural killer/T-cell lymphoma: diagnostic, prognostic and therapeutic implications

et al. 2020

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Natural killer/T-cell lymphoma (NKTCL) is an aggressive malignancy that usually presents in the upper aerodigestive tract. This malignancy shows substantial geographic variability in incidence, and is characterized by Epstein-Barr virus (EBV) infections. Epigenetic aberrations may dysregulate the expression of genes involved in different hallmarks of cancer. A growing body of evidence underscores the importance of epigenetic aberrations in the pathogenesis of NKTCL. Promoter hypermethylation is a common epigenetic mechanism for the inactivation of tumour suppressor genes. Several epigenetically silenced tumour suppressor candidates (e.g. PRDM1, BIM) were identified in this aggressive cancer using locus-specific and genome-wide promoter methylation analyses. Importantly, genes involved in epigenetic modifications were identified to be mutated (e.g. KMT2D) or methylated (e.g. TET2) in NKTCL patients, which may contribute to pathogenesis through global alterations in chromatin states. Cancer-associated microRNAs, some of which are expressed by EBV, and long noncoding RNAs have been observed to be dysregulated in NKTCL. This review focuses on studies investigating epigenetic aberrations in NKTCL to bolster our overall understanding of the role of these abnormalities in disease pathobiology. We also discuss the potential of these epigenetic aberrations to improve diagnosis and prognosis as well as reveal novel targets of therapy for NKTCL.

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Section: Noncoding Rnas In Nktcl Pathogenesismentioning

confidence: 99%

Epigenetic aberrations in natural killer/T-cell lymphoma: diagnostic, prognostic and therapeutic implications

et al. 2020

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“…Their contributions to viral pathogenesis and oncogenesis have been shown in many EBV-associated lymphomas [3,4]. Diverse cellular pathways including p53, B-cell signaling, immune activation, cell proliferation, and apoptosis are now known to be regulated by EBV miRNAs in lymphomas [5].…”

Section: Introductionmentioning

confidence: 99%

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-Barr Virus Associated Chronic Lymphocytic Leukemia

Kong

Wang

et al. 2020

Cancer Res Treat

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PurposeThe purpose of this study was to investigate the prognostic impact of Epstein-Barr virus (EBV)–microRNA (miRNA, miR)-BHRF1-1 with chronic lymphocytic leukemia (CLL) as well as role of EBV-miR-BHRF1-1 in p53 gene.Materials and MethodsQuantitative reverse transcription–polymerase chain reaction and western blotting were used to quantify EBV-miR-BHRF1-1 and p53 expression in cultured CLL.Resultsp53 aberration was associated with the higher expression level of EBV-miR-BHRF1-1 (p < 0.001) which was also an independent prognostic marker for overall survival (p=0.028; hazard ratio, 5.335; 95% confidence interval, 1.193 to 23.846) in 97 newly-diagnosed CLL patients after adjusted with International Prognostic Index for patients with CLL. We identified EBV-miR-BHRF1-1 as a viral miRNA regulator of p53. EBV-miR-BHRF1-1 repressed luciferase reporter activity by specific interaction with the seed region within the p53 3′- untranslated region. Discordance of p53 messenger RNA and protein expression was associated with high EBV-miR-BHRF1-1 levels in CLL patients and cell lines. EBV-miR-BHRF1- 1 inhibition upregulated p53 protein expression, induced cell cycle arrest and apoptosis and decreased cell proliferation in cell lines. EBV-miR-BHRF1-1 mimics downregulated p53 protein expression, decreased cell cycle arrest and apoptosis, and induced cell proliferation in cell lines.ConclusionThis study supported the role of EBV-miR-BHRF1-1 in p53 regulation in vitro. Our results support the potential of EBV-miR-BHRF1-1 as a therapeutic target in EBV-associated CLL with p53 gene aberration.

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“…The PI3K/Akt/mTor pathway plays an essential role in the oncogenic viral cycle, from entry to protein synthesis transcription, apoptosis inhibition and oncogenic transformation. Further recent studies of Epstein Barr virus [37] also suggest primary membrane-related mechanisms, but which remain to be explored.…”

Section: Resultsmentioning

confidence: 99%

Oncogenesis, lipids rafts and liquid crystals: A nanoscopic supplementary field for applied researches and a new hope of advances in cancer

Binot

Sadoc

2018

Heliyon

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Liquid crystals (LC) are an intermediate state between an ordered crystalline solid and a more disordered liquid. LCs (or mesophases) are ubiquitous in living systems, optimizing multiple biological functions that could not operate in purely solid or liquid environments as both mobility and organization are needed. One of us recently suggested that there is an information vector, shared by neurodegenerative and infectious pathologies, to be found within lipid rafts in an ordered liquid (Lo) form mediated by cholesterol. Here we extend this underlying mechanism to oncogenic processes. The specificity of our approach lies in highlighting the direct involvement of liquid crystals in early carcinogenic processes, by identifying specific metabolic pathways, with the intention of focusing research effort on this level, now that this has become technically feasible. Exploring LCs in living bodies reveals links between numerous oncogenic mechanisms. The approach is based on the geometric properties of amphiphilic (hydrophilic and lipophilic) plasma and intracellular membranes, the phospholipids of which are an example of the lamellar LC phase. These LCs underlie cell signaling and signaling pathways disorders at membrane level: consequently, they are directly concerned with deregulation underlying many cancerous processes.We demonstrate the implication of cancer cell membranes mesophases. That is in the membranes mesophases that are initiated most of metabolic pathways, leading to downstream pathogenic intracellular mechanisms. The concepts of order and of symmetry, in the mathematical sense, involved in condensed matter accompany informed adaptive supramolecular chemical processes in forming self-organizing mesogenic molecular assemblies. Multidisciplinary teamwork combining knowledge from different fields holds out the hope of therapeutic progress upstream of irreversible cancerous processes, while conserving the physiological integrity of the cells themselves.

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Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas

Cited by 33 publications

References 121 publications

Epigenetic aberrations in natural killer/T-cell lymphoma: diagnostic, prognostic and therapeutic implications

Epigenetic aberrations in natural killer/T-cell lymphoma: diagnostic, prognostic and therapeutic implications

EBV-miR-BHRF1-1 Targets p53 Gene: Potential Role in Epstein-Barr Virus Associated Chronic Lymphocytic Leukemia

Oncogenesis, lipids rafts and liquid crystals: A nanoscopic supplementary field for applied researches and a new hope of advances in cancer

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