title: Detection of circulating hcmv-miR-UL112-3p in patients with glioblastoma, rheumatoid arthritis, diabetes mellitus and healthy controls.
abstract: BACKGROUND
  microRNAs (miRNA) are 18-22 nucleotides long non-coding RNAs that regulate gene expression at a post-transcriptional level. Human cytomegalovirus (HCMV) encodes at least 26 known mature miRNAs. hcmv-miR-UL112-3p (miR-UL112-3p) is the most well characterized HCMV miRNA, which is suggested to play role in establishment and maintenance of viral latency. Elevated miR-UL112-3p levels have been reported to be present in plasma of patients with hypertension.
  
  
  OBJECTIVE
  In this study, we aimed to quantify miR-UL112-3p levels in the plasma/serum of patients with Diabetes Mellitus (DM; from the DIGAMI-2 cohort), Glioblastoma multiforme (GBM), Rheumatoid Arthritis (RA) and Healthy Controls (HC).
  
  
  METHODS
  Total RNA was isolated from plasma/serum samples of 87 patients and controls, a TaqMan miRNA assay was performed to detect miR-UL112-3p and the copy numbers were normalized to 10 ng of total RNA. HCMV IgG and IgM were analysed using ELISA.
  
  
  RESULTS
  HCMV miR-UL112-3p was detected in 14/27 (52%) of DM, 5/20 (25%) of GBM, 1/20 (5%) of RA patients and in 2/20 (10%) of HC, respectively. Anti-HCMV IgG was detected in 85%, 65%, 75% of patients and 70% of HC, respectively. Anti-HCMV IgM was found only in one GBM patient of 87 examined patients and controls.
  
  
  CONCLUSIONS
  A higher prevalence of miR-UL112-3p was detected in DM and GBM patients than in RA patients and HC. Elevated levels of miR-UL112-3p and higher prevalence of HCMV IgG were observed in DM patients. Whether the presence of circulating miR-UL112-3p denotes a biomarker of HCMV latency or active replication in patients warrants further investigation.
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine-Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Abdul-Aleem
authors.initials: AA
authors.lastname: Mohammad
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine-Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Afsar
authors.initials: A
authors.lastname: Rahbar
authors.affiliation: Department of Oncology-Pathology, Karolinksa Institutet, Cancer Center Karolinska, Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Weng-Onn
authors.initials: WO
authors.lastname: Lui
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine-Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Belghis
authors.initials: B
authors.lastname: Davoudi
authors.affiliation: Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anca
authors.initials: A
authors.lastname: Catrina
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine-Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Stragliotto
authors.affiliation: Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
authors.forename: Linda
authors.initials: L
authors.lastname: Mellbin
authors.affiliation: Atherosclerosis Research Unit, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Anders
authors.initials: A
authors.lastname: Hamsten
authors.affiliation: Cardiology Unit, Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Rydén
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine-Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Koon-Chu
authors.initials: KC
authors.lastname: Yaiw
authors.affiliation: Experimental Cardiovascular Research Unit, Department of Medicine-Solna, Center for Molecular Medicine, Karolinska Institute, Stockholm, Sweden.
authors.forename: Cecilia
authors.initials: C
authors.lastname: Söderberg-Nauclér
mesh_terms: D001172:Arthritis, Rheumatoid / Q000097:blood / Q000235:genetics* / Q000821:virology; D003587:Cytomegalovirus / Q000235:genetics* / Q000302:isolation & purification; D003586:Cytomegalovirus Infections / Q000235:genetics / Q000473:pathology / Q000821:virology; D003920:Diabetes Mellitus / Q000097:blood / Q000235:genetics* / Q000821:virology; D005260:Female; D015967:Gene Expression Regulation, Viral; D005909:Glioblastoma / Q000097:blood / Q000235:genetics* / Q000821:virology; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics* / Q000302:isolation & purification; D012367:RNA, Viral / Q000235:genetics / Q000302:isolation & purification; D017735:Virus Latency / Q000235:genetics; D014779:Virus Replication / Q000235:genetics
chemical_list: D035683:MicroRNAs; D012367:RNA, Viral; C000599836:microRNA-UL112, human cytomegalovirus