miR-483-5p plays a protective role in chronic obstructive pulmonary disease

Int J Mol Med. 2017 Jul;40(1):193-200. doi: 10.3892/ijmm.2017.2996. Epub 2017 May 18.

Abstract

Altered microRNA (miRNA or miR) expression has been reported in chronic obstructive pulmonary disease (COPD). The present study aimed to identify the involvement of miRNAs in the pathophysiology of COPD and to explore the effects of various miRNAs with significant alteration on COPD in vitro. We conducted high‑throughput analysis of miRNAs (miRNA microarray) in lung samples from 10 COPD patients and 10 healthy persons with a validation experiment using quantitative (real‑time) polymerase chain reaction (real‑time PCR) panels. By analyzing 3,000 miRNAs in lung samples using a microarray, we identified 341 differentially expressed miRNAs (138 with high expression and 203 with low expression) in patients with COPD in comparison with the healthy controls. Then 15 high-expression candidates and 15 low-expression candidates with at least 2‑fold difference and P<0.05 were selected randomly to validate the changes in three independent experiments in vitro using real‑time PCR. The validation test showed a positive correlation with the microarray results. Then we chose miR‑483‑5p as our target. The effect of miR‑483‑5p on cell proliferation and expression of COPD-related proteins were detected using Cell Counting Kit 8 and western blot analysis, respectively. The results showed that miR‑483‑5p, which was significantly downregulated in COPD samples, abrogated the transforming growth factor‑β (TGF‑β)‑mediated decrease in cell proliferation, and increase in α‑smooth muscle actin (α‑SMA) and fibronectin expression in pulmonary epithelial and lung fibroblast cell lines, BEAS‑2B and HFL1. These findings suggest that miR‑483‑5p may play an important and protective role in patients with COPD and may serve as a useful biomarker and for early detection of COPD as well as a potential therapeutic tool.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation*
  • Humans
  • Lung / metabolism*
  • Lung / pathology
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Oligonucleotide Array Sequence Analysis
  • Pulmonary Disease, Chronic Obstructive / metabolism*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / prevention & control

Substances

  • Biomarkers
  • MIRN483 microRNA, human
  • MicroRNAs