Bioinformatic analysis of microRNA and mRNA Regulation in peripheral blood mononuclear cells of patients with chronic obstructive pulmonary disease

Respir Res. 2017 Jan 5;18(1):4. doi: 10.1186/s12931-016-0486-5.

Abstract

Background: Chronic obstructive pulmonary disease (COPD) is a progressive, irreversible chronic inflammatory disorder typified by increased recruitment of monocytes, lymphocytes and neutrophils. Because of this, as well as the convenience of peripheral blood nuclear cells (PBMCs) assessments, miRNA profiling of PBMCs has drawn increasing attention in recent years for various disease. Therefore, we analyzed miRNA and mRNA profiles to understand their regulatory network between COPD subjects versus smokers without airflow limitation.

Methods: miRNA and mRNA profiling of PBMCs from pooled 17 smokers and 14 COPD subjects was detected by high-throughput microarray. The expression of dysregulated miRNAs were validated by q-PCR. The miRNA targets in dysregulated mRNAs were predicted and the pathway enrichment was analyzed.

Results: miRNA microarray showed that 8 miRNAs were up-regulated and 3 miRNAs were down-regulated in COPD subjects compared with smokers; the upregulation of miR-24-3p, miR-93-5p, miR-320a and miR-320b and the downregulation of miR-1273 g-3p were then validated. Bioinformatic analysis of regulatory network between miRNA and mRNA showed that NOD and TLR were the most enriched pathways. miR-24-3p was predicted to regulate IL-18, IL-1β, TNF, CCL3 and CCL4 and miR-93-5p to regulate IκBα.

Conclusions: The expression of miRNA and mRNA were dysregulated in PBMCs of COPD patients compared with smokers without airflow limitation. The regulation network between the dysregulated miRNA and mRNA may provide potential therapeutic targets for COPD.

Keywords: COPD; MicroRNA; Microarray; PBMC; miRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Computational Biology / methods
  • Female
  • Gene Expression Regulation / genetics*
  • Humans
  • Leukocytes, Mononuclear / metabolism*
  • Male
  • MicroRNAs / blood*
  • MicroRNAs / genetics
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / blood*
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • RNA, Messenger / blood*
  • RNA, Messenger / genetics
  • Smoking / metabolism*

Substances

  • MicroRNAs
  • RNA, Messenger