Upregulation of two human microRNAs which might be involved in the carcinogenesis of nasopharyngeal cancer and that are promising for biomarker development
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One of the biggest problems in diagnosing nasopharyngeal carcinoma (NPC) is the lack of biomarkers to detect the disease in its early stages. Thus, the exploration of biomarkers, which have the potential to be used to diagnose NPC in its early stages, is crucial. NPC is allegedly controlled by microRNAs (miRNAs); these molecules can be secreted out of cells and can be found in the serum—two aspects that make them potential biomarkers to be developed for non-invasive diagnosis of NPC. In this study, we analyzed the profile of miRNA expression in NPC biopsy tissue compared to normal tissues. The miRNA expression is taken from 246 samples of patients with NPC, compared to 17 samples from non-NPC subjects as the control. The results of the analysis identified more than 100 miRNAs that underwent an upregulation of expression in NPCs compared to that in the control group. Further analysis was focused on understanding the role of the miRNAs that were upregulated in NPCs. The results of this analysis reveal that there are six miRNAs: hsa-miR-1246, hsa-miR-320a, hsa-miR-1290, hsa-miR-146b-5p, hsa-miR-107, and hsa-miR-1305, which underwent increased expression and that are closely related to process of cancer (carcinogenesis) in NPC. Among the upregulated miRNA, the two miRNAs, miR-1290 and miR-1246, were found upregulated in the serum of NPC patients compared to the health persons. Moreover, the target genes of the miRNAs are also targets of the oncovirus protein that is involved in controlling the cell cycle and apoptosis. Upregulation of the miRNA might stimulate carcinogenesis through repressing guard genes for controlling cell cycle and apoptosis. The mechanism seems similar to the way the oncovirus initiates cancer.
KeywordsNPC Biomarker miRNA EBV Non-invasive diagnosis
We thank the Ministry of Research, Technology and higher education, republic of Indonesia for providing grant under scheme Hibah Stragnas-2017 No 063/SHP2H/LT/DRPM/IV/20017 to finish this study.
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The authors declare that they have no conflict of interest.
Research involving human participants and/or animals
This article does not contain any studies with human participants performed by any of the authors.
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Since this article does not involve human subject or animal object then we do not comply ethical clearance.
- Barrett T, Wilhite SE, Ledoux P, Evangelista C, Kim IF, Tomashevsky M, Marshall KA, Phillippy KH, Sherman PM, Holko M, Yefanov A, Lee H, Zhang N, Robertson CL, Serova N, Davis S, Soboleva A (2013) NCBI GEO: archive for functional genomics data sets—update. Nucleic Acids Res 41:D991–D995. https://doi.org/10.1093/nar/gks1193 CrossRefPubMedGoogle Scholar
- Bruce JP, Hui ABY, Shi W, Perez-Ordonez B, Weinreb I, Xu W, Haibe-Kains B, Waggott DM, Boutros PC, O’Sullivan B, Waldron J, Huang SH, Chen EX, Gilbert R, Liu FF (2015) Identification of a microRNA signature associated with risk of distant metastasis in nasopharyngeal carcinoma. Oncotarget 6:4537–4550. https://doi.org/10.18632/oncotarget.3005 CrossRefPubMedPubMedCentralGoogle Scholar
- Chawla JPS, Iyer N, Soodan KS, Sharma A, Khurana SK, Priyadarshni P (2015) Role of miRNA in cancer diagnosis, prognosis, therapy and regulation of its expression by Epstein–Barr virus and human papillomaviruses: with special reference to oral cancer. Oral Oncol 51:731–737. https://doi.org/10.1016/j.oraloncology.2015.05.008 CrossRefPubMedGoogle Scholar
- Deng L, Wang X, Jiang L, Yang J, Zhou X, Lu Z, Hu H (2016) Modulation of miR-185-5p expression by EBV-miR-BART6 contributes to developmental differences in ABCG4 gene expression in human megakaryocytes. Int J Biochem Cell Biol 81(Part A):105–111. https://doi.org/10.1016/j.biocel.2016.11.001 CrossRefPubMedGoogle Scholar
- Hartmann S, Döring C, Agostinelli C, Portscher-Kim SJ, Lonardi S, Lorenzi L, Fuligni F, Martinez D, Mehta J, Borges A, Hackstein H, Kippenberger S, Piccaluga PP, Simonitsch-Klupp I, Cabeçadas J, Campo E, Facchetti F, Pileri SA, Hansmann ML (2016) miRNA expression profiling divides follicular dendritic cell sarcomas into two groups, related to fibroblasts and myopericytomas or Castleman’s disease. Eur J Cancer 64:159–166. https://doi.org/10.1016/j.ejca.2016.06.004 CrossRefPubMedGoogle Scholar
- James CD, Roberts S (2016) Viral interactions with PDZ domain-containing proteins—an oncogenic trait? Pathogens 5:8. https://doi.org/10.3390/pathogens5010008
- Lu J, Tang M, Li H, Xu Z, Weng X, Li J, Yu X, Zhao L, Liu H, Hu Y, Tan Z, Yang L, Zhong M, Zhou J, Fan J, Bode AM, Yi W, Gao J, Sun L, Cao Y (2016) EBV-LMP1 suppresses the DNA damage response through DNA-PK/AMPK signaling to promote radioresistance in nasopharyngeal carcinoma. Cancer Lett 380:191–200. https://doi.org/10.1016/j.canlet.2016.05.032 CrossRefPubMedGoogle Scholar
- Peng J, Feng Y, Rinaldi G, Levine P, Easley S, Martinez E, Hashmi S, Sadeghi N, Brindley PJ, Mulvenna JP, Bethony JM, Plieskatt JL (2014) Profiling miRNAs in nasopharyngeal carcinoma FFPE tissue by microarray and next generation sequencing. Genom Data 2:285–289. https://doi.org/10.1016/j.gdata.2014.08.005 CrossRefPubMedPubMedCentralGoogle Scholar
- Plieskatt JL, Rinaldi G, Feng Y, Peng J, Yonglitthipagon P, Easley S, Laha T, Pairojkul C, Bhudhisawasdi V, Sripa B, Brindley PJ, Mulvenna JP, Bethony JM (2014) Distinct miRNA signatures associate with subtypes of cholangiocarcinoma from infection with the tumourigenic liver fluke Opisthorchis viverrini. J Hepatol 61:850–858. https://doi.org/10.1016/j.jhep.2014.05.035 CrossRefPubMedGoogle Scholar
- Rosales-Pérez S, Cano-Valdez AM, Flores-Balcázar CH, Guedea-Edo F, Lino-Silva LS, Lozano-Borbalas A, Navarro-Martín A, Poitevin-Chacón A (2014) Expression of Epstein-Barr virus-encoded latent membrane protein (LMP-1), p16 and p53 proteins in nonendemic nasopharyngeal carcinoma (NPC): a clinicopathological study. Arch Med Res 45:229–236. https://doi.org/10.1016/j.arcmed.2014.02.002 CrossRefPubMedGoogle Scholar
- Szklarczyk D, Franceschini A, Wyder S, Forslund K, Heller D, Huerta-Cepas J, Simonovic M, Roth A, Santos A, Tsafou KP, Kuhn M, Bork P, Jensen LJ, von Mering C (2015) STRING v10: protein–protein interaction networks, integrated over the tree of life. Nucleic Acids Res 43:D447–D452. https://doi.org/10.1093/nar/gku1003 CrossRefPubMedGoogle Scholar
- Topol A, Zhu S, Hartley BJ, English J, Hauberg ME, Tran N, Rittenhouse CA, Simone A, Ruderfer DM, Johnson J, Readhead B, Hadas Y, Gochman PA, Wang YC, Shah H, Cagney G, Rapoport J, Gage FH, Dudley JT, Sklar P, Mattheisen M, Cotter D, Fang G, Brennand KJ (2016) Dysregulation of miRNA-9 in a subset of schizophrenia patient-derived neural progenitor cells. Cell Rep 15:1024–1036. https://doi.org/10.1016/j.celrep.2016.03.090 CrossRefPubMedPubMedCentralGoogle Scholar
- Vlachos IS, Kostoulas N, Vergoulis T, et al (2012) DIANA miRPath v.2.0: investigating the combinatorial effect of microRNAs in pathways. Nucleic Acids Res 40:W498–504. https://doi.org/10.1093/nar/gks494
- Ye Y, Zhou Y, Zhang L, Chen Y, Lyu X, Cai L, Lu Y, Deng Y, Wang J, Yao K, Fang W, Cai H, Li X (2013) EBV-miR-BART1 is involved in regulating metabolism-associated genes in nasopharyngeal carcinoma. Biochem Biophys Res Commun 436:19–24. https://doi.org/10.1016/j.bbrc.2013.05.008 CrossRefPubMedGoogle Scholar