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MicroRNA in Epstein–Barr Virus-Associated Cancers
A conservative estimate suggests that almost 1.4 million of malignancies are associated with oncogenic viruses, including the hepatitis B virus, hepatitis C virus, Kaposi sarcoma-associated herpesvirus, human T lymphotropic virus type 1, human papillomaviruses, and Epstein–Barr virus (EBV). The oncogenic properties of these viruses are directly related to their ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. Among these viruses, EBV, formerly designated as the human herpesvirus type 4 (HHV-4), is a y-herpesvirus containing a linear, double-stranded DNA genome of ~172 kilobase pairs (kbp), encoding nearly 80 proteins and 46 functional small untranslated RNAs. The genetic material of EBV is enclosed in an icosahedral nucleocapsid surrounded by the viral tegument and lipid-containing outer envelope. EBV is transmitted through oral contact, particularly in the early years of life, usually without causing disease. EBV can also be transmitted through organ transplantation and blood transfusion. The life cycle of EBV primarily involves the infection of lymphocytes and potentially epithelial cells. Although EBV often exists as an asymptomatic infection, it is involved in the development of about 1.5% of all cancers worldwide. In fact, EBV was the first virus to have been directly associated with cancer in humans. EBV-associated neoplasms affect both immune-competent and immunocompromised hosts, including, for example, some organ transplant recipients. Immune dysregulation and genetic susceptibility are probable co-factors in most, if not all, EBV-associated cancers.
Epstein–Barr virus (EBV) is associated with a variety of malignancies. In this review, we discuss EBV-encoded microRNAs and ncRNAs and consider how their detection could aid in the diagnosis, prognostication, and monitoring of treatment in patients with EBV-associated malignancies, including classical Hodgkin’s lymphoma (cHL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBCL), nasopharyngeal carcinoma (NPC), and gastric carcinoma (GC).
EBV is a direct causative agent in around 1.5% of all cancers. The oncogenic properties of EBV are related to its ability to activate processes needed for cellular proliferation, survival, migration, and immune evasion. The EBV latency program is required for the immortalization of infected B cells and involves the expression of non-coding RNAs (ncRNAs), including viral microRNAs. These ncRNAs have different functions that contribute to virus persistence in the asymptomatic host and to the development of EBV-associated cancers. In this review, we discuss the function and potential clinical utility of EBV microRNAs and other ncRNAs in EBV-associated malignancies. This review is not intended to be comprehensive, but rather to provide examples of the importance of ncRNAs.
2. Epstein–Barr Virus
The entry is from 10.3390/cancers13153909
- de Martel, C.; Georges, D.; Bray, F.; Ferlay, J.; Clifford, G.M. Global burden of cancer attributable to infections in 2018: A worldwide incidence analysis. Lancet Glob. Health 2020, 8, e180–e190.
- de Elgui Oliveira, D.; Müller-Coan, B.G.; Pagano, J.S. Viral carcinogenesis beyond malignant transformation: EBV in the progression of human cancers. Trends Microbiol. 2016, 24, 649–664.
- Krump, N.A.; You, J. Molecular mechanisms of viral oncogenesis in humans. Nat. Rev. Microbiol. 2018, 16, 684–698.
- Wang, L.W.; Jiang, S.; Gewurz, B.E. Epstein-Barr virus LMP1-mediated oncogenicity. J. Virol. 2017, 91, e01718-16.
- Jenson, H.B. Epstein-Barr virus. Pediatr. Rev. 2011, 32, 375–383.
- Smatti, M.K.; Al-Sadeq, D.W.; Ali, N.H.; Pintus, G.; Abou-Saleh, H.; Nasrallah, G.K. Epstein-barr virus epidemiology, serology, and genetic variability of LMP-1 oncogene among healthy population: An update. Front. Oncol. 2018, 8.
- Farrell, P.J. Epstein–Barr virus and cancer. Annu. Rev. Pathol. Mech. Dis. 2019, 14, 29–53.
- Ko, Y.H. EBV and human cancer. Exp. Mol. Med. 2015, 47, e130.
- Guidry, J.T.; Birdwell, C.E.; Scott, R.S. Epstein–Barr virus in the pathogenesis of oral cancers. Oral Dis. 2018, 24, 497–508.
- Chen, J.; Longnecker, R. Epithelial cell infection by Epstein–Barr virus. FEMS MicroBiol. Rev. 2019, 43, 674–683.
- Tugizov, S.M.; Berline, J.W.; Palefsky, J.M. Epstein-Barr virus infection of polarized tongue and nasopharyngeal epithelial cells. Nat. Med. 2003, 9, 307–314.
- Shannon-Lowe, C.; Rowe, M. Epstein-Barr virus infection of polarized epithelial cells via the basolateral surface by memory B cell-mediated transfer infection. PLoS Pathog. 2011, 7, e1001338.
- Yin, H.; Qu, J.; Peng, Q.; Gan, R. Molecular mechanisms of EBV-driven cell cycle progression and oncogenesis. Med. MicroBiol. Immunol. 2019, 208, 573–583.
- Fernandez, A.F.; Rosales, C.; Lopez-Nieva, P.; Grana, O.; Ballestar, E.; Ropero, S.; Espada, J.; Melo, S.A.; Lujambio, A.; Fraga, M.F.; et al. The dynamic DNA methylomes of double-stranded DNA viruses associated with human cancer. Genome Res. 2009, 19, 438–451.
- Kang, M.S.; Kieff, E. Epstein-Barr virus latent genes. Exp. Mol. Med. 2015, 47.
- Zhao, M.; Nanbo, A.; Sun, L.; Lin, Z. Extracellular vesicles in Epstein-Barr virus’ life cycle and pathogenesis. Microorganisms 2019, 7, 48.
- Laichalk, L.L.; Thorley-Lawson, D.A. Terminal differentiation into plasma cells initiates the replicative cycle of Epstein-Barr virus in vivo. J. Virol. 2005, 79, 1296–1307.
- Reusch, J.A.; Nawandar, D.M.; Wright, K.L.; Kenney, S.C.; Mertz, J. Cellular differentiation regulator BLIMP1 induces Epstein–Barr virus lytic reactivation in epithelial and B cells by activating transcription from both the R and Z promoters. J. Virol. 2015, 89, 1731–1743.
- Howe, J.G.; Steitz, J.A. Localization of Epstein-Barr virus-encoded small RNAs by in situ hybridization. Proc. Natl. Acad. Sci. USA 1986, 83, 9006–9010.
- Clarke, P.A.; Sharp, N.A.; Clemens, M.J. Expression of genes for the Epstein-Barr virus small RNAs EBER-1 and EBER-2 in Daudi Burkitt’s lymphoma cells: Effects of interferon treatment. J. Gen. Virol. 1992, 73, 3169–3175.
- Wu, T.C.; Mann, R.B.; Charache, P.; Hayward, S.D.; Staal, S.; Lambe, B.C.; Ambinder, R.F. Detection of EBV gene expression in Reed-Sternberg cells of Hodgkin’s disease. Int. J. Cancer 1990, 46, 801–804.
- Lerner, M.R.; Andrews, N.C.; Miller, G.; Steitz, J.A. Two small RNAs encoded by Epstein-Barr virus and complexed with protein are precipitated by antibodies from patients with systemic lupus erythematosus. Proc. Natl. Acad. Sci. USA 1981, 78, 805–809.
- Toczyski, D.P.; Matera, A.G.; Ward, D.C.; Steitz, J.A. The Epstein-Barr virus (EBV) small RNA EBER1 binds and relocalizes ribosomal protein L22 in EBV-infected human B lymphocytes. Proc. Natl. Acad. Sci. USA 1994, 91, 3463–3467.
- Clemens, M.J.; Laing, K.G.; Jeffrey, I.W.; Schofield, A.; Sharp, T.V.; Elia, A.; Matys, V.; James, M.C.; Tilleray, V.J. Regulation of the interferon-inducible eIF-2 alpha protein kinase by small RNAs. Biochimie 1994, 76, 770–778.
- Gregorovic, G.; Boulden, E.A.; Bosshard, R.; Elgueta Karstegl, C.; Skalsky, R.; Cullen, B.R.; Gujer, C.; Rämer, P.; Münz, C.; Farrell, P.J. Epstein–Barr viruses (EBVs) deficient in EBV-encoded RNAs have higher levels of latent membrane protein 2RNAexpression in lymphoblastoid cell lines and efficiently establish persistent infections in humanized mice. J. Virol. 2015, 89, 11711–11714.
- Lee, N.; Moss, W.N.; Yario, T.A.; Steitz, J.A. EBV noncoding RNA binds nascent RNA to drive host PAX5 to viral DNA. Cell 2015, 160, 607–618.
- Kheimar, A.; Kaufer, B.B. Epstein-Barr virus-encoded RNAs (EBERs) complement the loss of herpesvirus telomerase RNA (vTR) in virus-induced tumor formation. Sci. Rep. 2018, 8, 209.
- Calin, G.A.; Croce, C.M. MicroRNA-cancer connection: The beginning of a new tale. Cancer Res. 2006, 66, 7390–7394.
- Macfarlane, L.A.; Murphy, P.R. MicroRNA: Biogenesis; Function and Role in Cancer. Curr. Genom. 2010, 11, 537–561.
- Jansson, M.D.; Lund, A.H. MicroRNA and cancer. Mol. Oncol. 2012, 6, 590–610.
- Lin, S.; Gregory, R.I. MicroRNA biogenesis pathways in cancer. Nat. Rev. Cancer 2015, 15, 321–333.
- Di Leva, G.; Croce, C.M. miRNA profiling of cancer. Curr. Opin. Genet. Dev. 2013, 23, 3–11.
- Eis, P.S.; Tam, W.; Sun, L.; Chadburn, A.; Li, Z.; Gomez, M.F.; Lund, E.; Dahlberg, J.E. Accumulation of miR-155 and BIC RNA in human B cell lymphomas. Proc. Natl. Acad. Sci. USA 2005, 102, 3627–3632.
- Cimmino, A.; Calin, G.A.; Fabbri, M.; Iorio, M.V.; Ferracin, M.; Shimizu, M.; Wojcik, S.E.; Aqeilan, R.I.; Zupo, S.; Dono, M.; et al. miR-15 and miR-16 induce apoptosis by targeting BCL2. Proc. Natl. Acad. Sci. USA 2005, 102, 13944–13949.
- Yanaihara, N.; Caplen, N.; Bowman, E.; Seike, M.; Kumamoto, K.; Yi, M.; Stephens, R.M.; Okamoto, A.; Yokota, J.; Tanaka, T.; et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell 2006, 9, 189–198.
- Hayashita, Y.; Osada, H.; Tatematsu, Y.; Yamada, H.; Yanagisawa, K.; Tomida, S.; Yatabe, Y.; Kawahara, K.; Sekido, Y.; Takahashi, T. A polycistronic microRNA cluster, miR-17-92, is overexpressed in human lung cancers and enhances cell proliferation. Cancer Res. 2005, 65, 9628–9632.
- Moi, L.; Braaten, T.; Al-Shibli, K.; Lund, E.; Busund, L.T.R. Differential expression of the miR-17-92 cluster and miR-17 family in breast cancer according to tumor type; results from the Norwegian Women and Cancer (NOWAC) study. J. Transl. Med. 2019, 17, 334.
- Gupta, R.; Shah, N.; Wang, K.; Kim, J.; Horlings, H.M.; Wong, D.J.; Tsai, M.C.; Hung, T.; Argani, P.; Rinn, J.L.; et al. Long non-coding RNA HOTAIR reprograms chromatin state to promote cancer metastasis. Nature 2010, 464, 1071–1076.
- Ji, P.; Diederichs, S.; Wang, W.; Böing, S.; Metzger, R.; Schneider, P.M.; Tidow, N.; Brandt, B.; Buerger, H.; Bulk, E.; et al. MALAT-1, a novel noncoding RNA, and thymosin beta4 predict metastasis and survival in early-stage non-small cell lung cancer. Oncogene 2003, 22, 8031–8041.
- Xu, C.; Yang, M.; Tian, J.; Wang, X.; Li, Z. MALAT-1: A long non-coding RNA and its important 3’ end functional motif in colorectal cancer metastasis. Int. J. Oncol. 2011, 39, 169–175.
- Reddy, K.B. MicroRNA (miRNA) in cancer. Cancer Cell Int. 2015, 15.
- Kosaka, N.; Iguchi, H.; Ochiya, T. Circulating microRNA in body fluid: A new potential biomarker for cancer diagnosis and prognosis. Cancer Sci. 2010, 101, 2087–2092.