title: Overexpression of blood microRNAs 103a, 30b, and 29a in L-dopa-treated patients with PD.
abstract: OBJECTIVE
  The aims of the present study were to profile the expression of several candidate microRNAs (miRNAs) in blood from L-dopa-treated and drug-naive patients with Parkinson disease (PD) vs unaffected controls and to interpret the miRNA expression data in a biological context.
  
  
  METHODS
  We analyzed RNAs from peripheral blood of 36 L-dopa-treated, 10 drug-naive patients with PD and unaffected controls matched 1:1 by sex and age. We evaluated expression by reverse transcription-quantitative real-time PCR, and we analyzed data using a 2-tailed paired t test. To detect miRNA targets, several miRNA resources were combined to generate an overall score for each candidate gene using weighted rank aggregation.
  
  
  RESULTS
  Significant overexpression of miR-103a-3p (p < 0.0001), miR-30b-5p (p = 0.002), and miR-29a-3p (p = 0.005) in treated patients with PD was observed, and promising candidate target genes for these were revealed by an integrated in silico analysis.
  
  
  CONCLUSIONS
  We revealed 3 candidate biomarkers for PD. miRNAs 30b-5p and 29a-3p replicated a documented deregulation in PD albeit opposite to published data, while for miR-103a-3p, we demonstrated for the first time an overexpression in treated patients with PD. Expression studies in patients and/or in isolated peripheral blood mononuclear cells before and after L-dopa administration are necessary to define the involvement of L-dopa treatment in the observed overexpression. Our in silico analysis to prioritize targets of deregulated miRNAs identified candidate target genes, including genes related to neurodegeneration and PD. Despite the preliminary character of our study, the results provide a rationale for further clarifying the role of the identified miRNAs in the pathogenesis of PD and for validating their diagnostic potential.
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Alice
authors.initials: A
authors.lastname: Serafin
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Luisa
authors.initials: L
authors.lastname: Foco
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Stefano
authors.initials: S
authors.lastname: Zanigni
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Hagen
authors.initials: H
authors.lastname: Blankenburg
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Anne
authors.initials: A
authors.lastname: Picard
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Zanon
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Giulia
authors.initials: G
authors.lastname: Giannini
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Irene
authors.initials: I
authors.lastname: Pichler
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Maurizio F
authors.initials: MF
authors.lastname: Facheris
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Pietro
authors.initials: P
authors.lastname: Cortelli
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Hicks
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany.
authors.forename: Francisco S
authors.initials: FS
authors.lastname: Domingues
authors.affiliation: From the Center for Biomedicine (A.S., L.F., S.Z., H.B., A.P., A.Z., G.G., I.P., M.F.F., P.P.P., A.A.H., F.S.D., C.S.), European Academy Bozen/Bolzano (EURAC), Bolzano, Italy, affiliated institute of the University of Lübeck, Germany; Department of Neurology (S.Z., P.P.P.), General Central Hospital, Bolzano; IRCCS Institute of Neurological Sciences of Bologna (P.C.); Department of Biomedical and NeuroMotor Sciences (P.C.), Alma Mater Studiorum-University of Bologna, Italy; Department of Neurology (P.P.P.), University of Lübeck, Germany. christine.schwienbacher@eurac.edu.
authors.forename: Christine
authors.initials: C
authors.lastname: Schwienbacher
mesh_terms: D000368:Aged; D000978:Antiparkinson Agents / Q000627:therapeutic use*; D054316:Biomarkers, Pharmacological / Q000097:blood; D003198:Computer Simulation; D005260:Female; D006801:Humans; D007980:Levodopa / Q000627:therapeutic use*; D008297:Male; D035683:MicroRNAs / Q000097:blood*; D010300:Parkinson Disease / Q000097:blood* / Q000188:drug therapy; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D000978:Antiparkinson Agents; D054316:Biomarkers, Pharmacological; C544749:MIRN103 microRNA, human; C532045:MIRN29a microRNA, human; C546086:MIRN30b microRNA, human; D035683:MicroRNAs; D007980:Levodopa