title: Inverse correlation of expression of microRNA-140-5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells.
abstract: The role of microRNA in the regulation of encephalitogenic T-cell development is of interest in understanding the pathogenesis of multiple sclerosis (MS). Direct binding of microRNAs to their target mRNAs usually suppresses gene expression and facilitates mRNA degradation. In this study, we observed that the expression of several microRNAs was significantly altered in patients with MS. Interestingly, the expression of miR-140-5p, among other microRNAs, was significantly decreased in the peripheral blood mononuclear cells of patients with MS, and this microRNA may regulate encephalitogenic T helper type 1 (Th1) cell differentiation. The expression level of miR-140-5p was inversely correlated with disease severity with greater reduction in relapsing disease compared with remitting disease. Transfection of synthetic miR-140-5p in peripheral blood mononuclear cells suppressed encephalitogenic Th1 differentiation. Signal transducer and activator of transcription 1 (STAT1) was the functional target of miR-140-5p - transfection of the synthetic miR-140-5p suppressed activation of STAT1 and the expression of its downstream target, T-bet. Our results suggested that miR-140-5p is probably involved in the regulation of encephalitogenic T cells in the pathogenesis of MS.
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.|Key Laboratory of Oral Medicine, Guangzhou Institute of Oral Disease, Stomatology Hospital of Guangzhou Medical University, Guangzhou, China.
authors.forename: Hongbing
authors.initials: H
authors.lastname: Guan
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Udai P
authors.initials: UP
authors.lastname: Singh
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Roshni
authors.initials: R
authors.lastname: Rao
authors.affiliation: Department of Neurology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Davit
authors.initials: D
authors.lastname: Mrelashvili
authors.affiliation: Department of Neurology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Souvik
authors.initials: S
authors.lastname: Sen
authors.affiliation: Deep Sequencing and Microarray Core, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: Haiping
authors.initials: H
authors.lastname: Hao
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Zumbrun
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Narendra P
authors.initials: NP
authors.lastname: Singh
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Nagarkatti
authors.affiliation: Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC, USA.|WJB Dorn Veterans Affairs Medical Center, Columbia, SC, USA.
authors.forename: Mitzi
authors.initials: M
authors.lastname: Nagarkatti
mesh_terms: D000328:Adult; D001483:Base Sequence; D001665:Binding Sites; D016022:Case-Control Studies; D002454:Cell Differentiation / Q000235:genetics / Q000276:immunology; D016000:Cluster Analysis; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics / Q000378:metabolism; D008297:Male; D035683:MicroRNAs / Q000737:chemistry / Q000235:genetics*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000235:genetics / Q000276:immunology / Q000473:pathology; D034622:RNA Interference; D050794:STAT1 Transcription Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D020825:T-Box Domain Proteins / Q000235:genetics; D018417:Th1 Cells / Q000166:cytology / Q000276:immunology* / Q000378:metabolism*; D015533:Transcriptional Activation; D000098815:T-bet Transcription Factor
chemical_list: D035683:MicroRNAs; C544302:Mirn140 microRNA, human; D050794:STAT1 Transcription Factor; D020825:T-Box Domain Proteins; D000098815:T-bet Transcription Factor; C487931:mirnlet7 microRNA, human; D007371:Interferon-gamma
keywords: Th1/Th2 cells; cell differentiation; miR-140-5p; microRNA; multiple sclerosis