title: Dicer and microRNA expression in multiple sclerosis and response to interferon therapy.
abstract: Dysregulation of microRNA expression has been shown in multiple sclerosis (MS); however, the mechanisms underlying these changes, their response to therapy and the impact of microRNA changes in MS are not completely understood. Dicer mediates the cleavage of precursor microRNAs to mature microRNAs and is dysregulated in multiple pathologies. Having shown that interferons regulate Dicer in vitro, we hypothesized that MS patient IFNβ1a treatment could potentially alter Dicer expression. Dicer mRNA and protein levels, as well as microRNA expression, were determined in MS patient and healthy control PBL. Acute responses to IFNβ1a were assessed in 50 patients. We found that Dicer protein but not mRNA levels decreases in MS patients while both are selectively induced in patients responding well to IFNβ1a. Potential microRNA biomarkers for relapsing remitting multiple sclerosis (RRMS), secondary progressive multiple sclerosis (SPMS) and IFNβ1a response are described. Contrasts in Dicer and microRNA expression levels between patient populations may offer insight into mechanisms underlying disease courses and responses to IFNβ1a therapy. This work identifies Dicer regulation as both a potential mediator of MS pathology and a therapeutic target.
authors.affiliation: Laboratory of Molecular Medicine, Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA; Department of Microbiology and Immunology, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA. Electronic address: william.magner@roswellpark.org.
authors.forename: William J
authors.initials: WJ
authors.lastname: Magner
authors.affiliation: Jacobs Neurological Institute, Buffalo, NY, USA; Department of Neurology, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA. Electronic address: BWeinstock-Guttman@KaleidaHealth.Org.
authors.forename: Bianca
authors.initials: B
authors.lastname: Weinstock-Guttman
authors.affiliation: Division of Computer Science and Engineering, Hanyang University, Seoul, Republic of Korea. Electronic address: minarho@hanyang.ac.kr.
authors.forename: Mina
authors.initials: M
authors.lastname: Rho
authors.affiliation: Jacobs Neurological Institute, Buffalo, NY, USA; Department of Neurology, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA. Electronic address: DHojnacki@KaleidaHealth.Org.
authors.forename: David
authors.initials: D
authors.lastname: Hojnacki
authors.affiliation: Jacobs Neurological Institute, Buffalo, NY, USA; Department of Neurology, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA. Electronic address: rabiagha@buffalo.edu.
authors.forename: Rabia
authors.initials: R
authors.lastname: Ghazi
authors.affiliation: Jacobs Neurological Institute, Buffalo, NY, USA; Department of Neurology, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA; Department of Pharmaceutical Sciences, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA. Electronic address: murali@buffalo.edu.
authors.forename: Murali
authors.initials: M
authors.lastname: Ramanathan
authors.affiliation: Laboratory of Molecular Medicine, Department of Immunology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA; Department of Microbiology and Immunology, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA; Department of Medicine, State University of New York, School of Medicine and Biomedical Sciences, Buffalo, NY, USA. Electronic address: thomas.tomasi@roswellpark.org.
authors.forename: Thomas B
authors.initials: TB
authors.lastname: Tomasi
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D016022:Case-Control Studies; D053487:DEAD-box RNA Helicases / Q000378:metabolism*; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D000068556:Interferon beta-1a / Q000627:therapeutic use*; D008297:Male; D035683:MicroRNAs / Q000378:metabolism*; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D043244:Ribonuclease III / Q000378:metabolism*; D013223:Statistics as Topic; D018709:Statistics, Nonparametric
chemical_list: D000970:Antineoplastic Agents; D035683:MicroRNAs; D012333:RNA, Messenger; C408087:DICER1 protein, human; D043244:Ribonuclease III; D053487:DEAD-box RNA Helicases; D000068556:Interferon beta-1a
keywords: Biomarkers; Dicer; Interferon; MicroRNA; Multiple sclerosis; Therapy