title: The identification of up-regulated ebv-miR-BHRF1-2-5p targeting MALT1 and ebv-miR-BHRF1-3 in the circulation of patients with multiple sclerosis.
abstract: Epstein-Barr virus (EBV) is a well-documented aetiological factor for multiple sclerosis (MS). EBV encodes at least 44 microRNAs (miRNAs) that are readily detectable in the circulation of human. Previous studies have demonstrated that EBV-encoded miRNAs regulate host immune response and may serve as biomarkers for EBV-associated diseases. However, the roles of EBV miRNAs in MS are still unknown. To fill the gap, we conducted a comprehensive profiling of 44 mature EBV miRNAs in 30 relapsing-remitting MS (RRMS) patients at relapse and 30 matched healthy controls. Expression levels of ebv-miR-BHRF1-2-5p and ebv-miR-BHRF1-3 were elevated significantly in the circulation and correlated positively with the expanded disability status scale (EDSS) scores of MS patients. Receiver operating characteristic (ROC) analyses confirmed that the expression of these two miRNAs distinguished MS patients clearly from healthy controls. Luciferase assays revealed that ebv-miR-BHRF1-2-5p may directly target MALT1 (mucosa-associated lymphoid tissue lymphoma transport protein 1), a key regulator of immune homeostasis. In conclusion, we described the expression of EBV miRNAs in MS and preliminarily validated the potential target genes of significantly altered EBV miRNAs. The findings may pave the way for prospective study about the pathogenesis of MS.
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: Y F
authors.initials: YF
authors.lastname: Wang
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: D D
authors.initials: DD
authors.lastname: He
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: H W
authors.initials: HW
authors.lastname: Liang
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: D
authors.initials: D
authors.lastname: Yang
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: H
authors.initials: H
authors.lastname: Yue
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: X M
authors.initials: XM
authors.lastname: Zhang
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: R
authors.initials: R
authors.lastname: Wang
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: B
authors.initials: B
authors.lastname: Li
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: H X
authors.initials: HX
authors.lastname: Yang
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: Y X
authors.initials: YX
authors.lastname: Duan
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Zhang
authors.affiliation: Jiangsu Engineering Research Center for microRNA Biology and Biotechnology, School of Life Sciences, Nanjing University, Nanjing, Jiangsu, China.
authors.forename: X
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurology, the Second Affiliated Hospital of Harbin Medical University, Harbin Medical University, Harbin, China.
authors.forename: J
authors.identifier: 0000-0002-4792-8813
authors.initials: J
authors.lastname: Fu
mesh_terms: D000293:Adolescent; D000328:Adult; D016022:Case-Control Studies; D020169:Caspases / Q000235:genetics*; D002681:China; D020031:Epstein-Barr Virus Infections / Q000150:complications*; D005260:Female; D004854:Herpesvirus 4, Human; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein; D009103:Multiple Sclerosis / Q000097:blood*; D009363:Neoplasm Proteins / Q000235:genetics*; D011446:Prospective Studies; D012372:ROC Curve; D015533:Transcriptional Activation; D015854:Up-Regulation; D014764:Viral Proteins / Q000097:blood* / Q000235:genetics; D055815:Young Adult
chemical_list: C083278:BHRF1 protein, Human herpesvirus 4; D035683:MicroRNAs; D009363:Neoplasm Proteins; D014764:Viral Proteins; D020169:Caspases; C400109:MALT1 protein, human; D000074884:Mucosa-Associated Lymphoid Tissue Lymphoma Translocation 1 Protein
keywords: Epstein-Barr virus; MALT1; microRNA; multiple sclerosis