Detection of circulating hcmv-miR-UL112-3p in patients with glioblastoma, rheumatoid arthritis, diabetes mellitus and healthy controls

PLoS One. 2014 Dec 2;9(12):e113740. doi: 10.1371/journal.pone.0113740. eCollection 2014.

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.

Objectives: 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).

Study design: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / genetics*
  • Arthritis, Rheumatoid / virology
  • Cytomegalovirus / genetics*
  • Cytomegalovirus / isolation & purification
  • Cytomegalovirus Infections / genetics
  • Cytomegalovirus Infections / pathology
  • Cytomegalovirus Infections / virology
  • Diabetes Mellitus / blood
  • Diabetes Mellitus / genetics*
  • Diabetes Mellitus / virology
  • Female
  • Gene Expression Regulation, Viral
  • Glioblastoma / blood
  • Glioblastoma / genetics*
  • Glioblastoma / virology
  • Humans
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / isolation & purification
  • RNA, Viral / genetics
  • RNA, Viral / isolation & purification
  • Virus Latency / genetics
  • Virus Replication / genetics

Substances

  • MicroRNAs
  • RNA, Viral
  • microRNA-UL112, human cytomegalovirus

Grants and funding

This study was funded by: Sten A Olssons Foundation for Research and Culture, Erling-Persson Family Foundation, Torsten Soderberg Foundation, BILTEMA Foundation, lngaBritt and Arne Lundbergs Foundation, Stichting af Jochnick Foundation, Jane and Dan Olssons Research Foundation, Petrus and Augusta Hedlund Foundation, nxt2b, RATOS, Swedish Cancer Foundation, Children's Cancer Foundation, Swedish Medical Research Council, Thematic Research Center and Stockholm County Council, Swedish Heart-Lung Foundation, Bayer and Karolinska Institution's Foundation. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.