Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas
Abstract
:1. Epstein–Barr Virus as an Oncovirus in Human Lymphomas
EBV Latency Programs
2. MicroRNAs
3. EBV-Encoded MicroRNAs in Human Lymphomas
3.1. EBV miRNA Expression Patterns
3.2. Pathologic and Biologic Role of EBV miRNAs
3.2.1. EBV miRNAs Contribute to Evasion from Immunosurveillance
3.2.2. EBV miRNAs Interfere with Several Other Cancer-Related Mechanisms
3.2.3. Molecular Networks and Circuits Define More Complex Roles for EBV-Encoded MicroRNAs
3.2.4. The Pathogenetic Effect of Viral miRNAs Could Be Observed at Global Gene Expression Profile Level
3.2.5. Exosomal Shuttle MicroRNAs Help EBV to Manipulate Its Surrounding Microenvironment
3.3. EBV miRNAs as Molecular Markers for Classification, Diagnosis, and Prognosis
4. Conclusion Remarks
Acknowledgments
Conflicts of Interest
Abbreviations
BART | BamHI-A rightward transcript |
BAX | BCL2 Associated X |
BHRF1 | BamHI fragment H rightward open reading frame 1 |
BL | Burkitt Lymphoma |
CASP3 | Caspase 3 |
CDKN1B | Cyclin Dependent Kinase Inhibitor 1b |
C/EBP | CCAAT-Enhancer-Binding Protein |
CLL | Chronic Lymphocytic Leukemia |
CREBBP | CREB-Binding Protein |
CTSB | cathepsin B |
Cp | C Promoter |
DLBCL | Diffuse Large B Cell Lymphoma |
EBERs | EBV-Encoded small RNAs |
eBL | endemic Burkitt Lymphoma |
EBNA | EBV-Encoded Nuclear Antigen |
EBNA-LP | EBV-Encoded Nuclear Antigen Leader Protein |
EBV | Epstein–Barr Virus |
HHV-4 | Human Herpesvirus 4 |
HIV-BL | HIV-related Burkitt Lymphoma |
HIV-DLBCL | HIV-related Diffuse Large B Cell Lymphoma |
HL | Hodgkin Lymphoma |
IFI30 | Interferon Gamma Inducible Protein 30 |
IFN | Interferon |
IgG | Immunoglobulin G |
IHC | Immunohistochemistry |
IL-1 | Interleukin-1 |
IL-1β | Interleukin-1β |
IL-12B | Interleukin-12 Subunit Beta |
IL-18 | Interleukin 18 |
IL-6 | Interleukin-6 |
IL-6RB | Interleukin-6 Receptor B |
IPO7 | Importin 7 |
IRF | Interferon Regulatory Factor |
ISH | In Situ Hybridization |
LCL | Lymphoblastoid Cell Line |
LGMN | Legumain |
LMP | Latent Membrane Protein |
MHC | Major Histocompatibility Complex |
miRNA | microRNA |
MTX-LPD | Methotrexate-Associated Lymphoproliferative Disorder |
NKTL | Natural Killer/T Cell Lymphoma |
NLRP3 | NLR Family Pyrin Domain Containing 3 |
p27 | protein 27 |
P1 | Promoter 1 |
P2 | Promoter 2 |
PAL | Pyothorax-Associated Lymphoma |
PBL | Plasmablastic Lymphoma |
PRDM1 | pr/set domain 1 |
PTEN | Phosphatase and Tensin Homolog |
PTLD | Post-Transplant Lymphoproliferative Disorder |
Qp | Q Promoter |
RICTOR | Rapamycin-Insensitive Companion of Mammalian Target of Rapamycin |
RIG-I | Retinoic-Acid-Inducible Protein 1 |
S1PR1 | Sphingosin-1-Phosphate Receptor 1 |
sBL | sporadic Burkitt Lymphoma |
SNP | Single Nucleotide Polymorphism |
SUMO | Small Ubiquitin-Like Modifier |
TAP | Transporter Associated With Antigen Processing |
T-bet | T-box Protein Expressed in T cells |
TOMM22 | Translocase of Outer Mitochondrial Membrane 22 |
VEGFA | Vascular Endothelial Growth Factor A |
Wp | W Promoter |
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Latency Type | Expressed Product | Example | Reference |
---|---|---|---|
Type I | EBNA1, EBERs, BART miRNAs | BL, MTX-LPD, PBL | [9,23,24] |
Type II | EBNA1, LMP1, LMP2s, EBERs, BART miRNAs | HL, PBL, MTX-LPD, NKTL, CLL, PTLD, DLBCL of the elderly | [6,23,24,25,26,27,28] |
Type III | EBNA1, EBNA2, EBNA3s, LMP1, LMP2s, EBERs, BART miRNAs (non-to-low), BHRF1 | PTLD, DLBCL of elderly, PAL, HIV-DLBCL, LCL | [3,8,28] |
MicroRNA | Target | Related Process/Application | Reference |
---|---|---|---|
BART and BHRF1 Families | EBNA1 | Latency Regulation | [77] |
BHRF1 Family | PTEN | Cell Proliferation, Apoptosis | [87] |
p27 | Cell Cycle Progression | [87] | |
Unidentified | Transformation Capacity, Cell Cycle Progression | [79] | |
Unidentified | Acute Systemic EBV Infection | [94] | |
Latent Proteins | Latency Regulation | [79] | |
miR-BHRF1-1 | Not Applicable | Survival Marker in CLL | [10] |
miR-BHRF1-2 | CTSB | CD4+ T Cell Response | [77,78] |
PRDM1 | Cell Cycle Progression, Apoptosis | [85] | |
IL-12B | CD4+ T Cell Response | [77,78] | |
miR-BHRF1-2-5p | IL-1 receptor | Innate Immunity | [75] |
miR-BHRF1-3 | TAP2 | CD8+ T Cell Response | [77,78] |
miR-BART1-3p | IL-12B | CD4+ T Cell Response | [77,78] |
IFI30 | CD4+ T Cell Response | [77,78] | |
CASP3 | Apoptosis | [72] | |
miR-BART1-5p | IFI30 | CD4+ T-Cell Response | [77,78] |
CASP3 | Apoptosis | [84] | |
Not Applicable | Diagnostic Marker for NKTL | [11] | |
miR-BART2-5p | CTSB | CD4+ T-Cell Response | [77,78] |
LGMN | CD4+ T-Cell Response | [77,78] | |
IL-12B | CD4+ T-Cell Response | [77,78] | |
CASP3 | Apoptosis | [84] | |
BALF5 | Latency Regulation | [80] | |
Not Applicable | Diagnostic Marker for NKTL | ||
miR-BART3-3p | IPO7 | Innate Immunity | [72,74] |
CASP3 | Apoptosis | [84] | |
miR-BART4-5p | CASP3 | Apoptosis | [84] |
miR-BART6-3p | PTEN * | Cell Proliferation, Apoptosis | [86] |
IL-6RB ** | Innate Immunity | [71] | |
RIG-I | Innate Immunity | [68] | |
miR-BART7-3p | CASP3 | Apoptosis | [84] |
Not Applicable | Diagnostic Marker for NKTL | [11] | |
miR-BART8-5p | CASP3 | Apoptosis | [84] |
miR-BART10-3p | IL-12B | CD4+ T Cell Response | [77,78] |
miR-BART13-3p | CASP3 | Apoptosis | [84] |
Not Applicable | Diagnostic Marker for NKTL | [11] | |
miR-BART15 | NLRP3 | Innate Immunity | [70] |
miR-BART16 | S1PR1 | Cell Growth/Mobility *** | [48] |
CREBBP | Innate Immunity | [76] | |
IPO7 | Innate Immunity | [72] | |
CASP3 | Apoptosis | [72] | |
TOMM22 | Apoptosis | [74] | |
miR-BART17 | TAP2 | CD8+ T-Cell Response | [77] |
miR-BART20-5p | T-bet **** | Transcription Regulation of Cytotoxic NK Cells | [92] |
miR-BART22 | CASP3 | Apoptosis | [84] |
IL-12B | CD4+ T Cell Response | [77,78] |
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Navari, M.; Etebari, M.; Ibrahimi, M.; Leoncini, L.; Piccaluga, P.P. Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas. Int. J. Mol. Sci. 2018, 19, 1168. https://doi.org/10.3390/ijms19041168
Navari M, Etebari M, Ibrahimi M, Leoncini L, Piccaluga PP. Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas. International Journal of Molecular Sciences. 2018; 19(4):1168. https://doi.org/10.3390/ijms19041168
Chicago/Turabian StyleNavari, Mohsen, Maryam Etebari, Mostafa Ibrahimi, Lorenzo Leoncini, and Pier Paolo Piccaluga. 2018. "Pathobiologic Roles of Epstein–Barr Virus-Encoded MicroRNAs in Human Lymphomas" International Journal of Molecular Sciences 19, no. 4: 1168. https://doi.org/10.3390/ijms19041168