Peripheral leukocyte microRNAs as novel biomarkers for COPD

Int J Chron Obstruct Pulmon Dis. 2017 Apr 6:12:1101-1112. doi: 10.2147/COPD.S130416. eCollection 2017.

Abstract

COPD is a multifactorial disease caused by environmental determinants as well as genetic risk factors. The prevalence and mortality of COPD continue to increase, and underdiagnosis of COPD remains a critical issue. Previous reports investigated promising microRNAs (miRNAs) to reveal the molecular mechanism for the development of COPD; however, diagnostic and therapeutic markers for COPD have not yet been found. For this study, 20 representative COPD patients were separated into four groups based on increasing severity (A, B, C, and D) and compared to six healthy controls. Small RNA profiles of peripheral leukocytes were differentially expressed miRNAs (analyzed via next-generation sequencing) were validated via quantitative reverse transcriptase-polymerase chain reaction. Compared to healthy controls, 19 differentially expressed miRNAs were found in COPD patients. For all COPD groups, miR-3177-3p was downregulated, while 17 miRNAs were upregulated. Furthermore, the results revealed 21 differentially expressed miRNAs, of which miR-183-5p was continually downregulated from A to B to D. Between respective bronchodilator reversibility positive and negative groups of COPD different groups (A, B, C, and D), 10 miRNAs were differentially expressed, while miR-100-5p was upregulated in the negative groups. In conclusion, miR-106b-5p, miR-125a-5p, miR-183-5p, and miR-100-5p are central for the development of COPD. The severity of COPD was attenuated by miR-106b-5p, thus suggesting this miRNA as potential target for disease treatment.

Keywords: COPD; diagnosis; miRNA; qRT-PCR; sequencing.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Case-Control Studies
  • Circulating MicroRNA / blood
  • Circulating MicroRNA / genetics*
  • Cross-Sectional Studies
  • Female
  • Gene Expression Profiling / methods
  • Genetic Markers
  • Genetic Predisposition to Disease
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Leukocytes / chemistry*
  • Male
  • MicroRNAs / blood
  • MicroRNAs / genetics
  • Middle Aged
  • Phenotype
  • Predictive Value of Tests
  • Pulmonary Disease, Chronic Obstructive / blood
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Real-Time Polymerase Chain Reaction
  • Reproducibility of Results
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcriptome

Substances

  • Circulating MicroRNA
  • Genetic Markers
  • MIRN100 microRNA, human
  • MIRN106 microRNA, human
  • MIRN125 microRNA, human
  • MIRN185 microRNA, human
  • MicroRNAs