MiR-221-3p and miR-92a-3p enhances smoking-induced inflammation in COPD

J Clin Lab Anal. 2021 Jul;35(7):e23857. doi: 10.1002/jcla.23857. Epub 2021 Jun 7.

Abstract

Background: Smoking is likely to facilitate airway inflammation and finally contributes to chronic obstructive pulmonary disease (COPD). This investigation was intended to elucidate miRNAs that were involved in smoking-induced COPD.

Methods: Altogether 155 COPD patients and 77 healthy volunteers were recruited, and their serum levels of miR-221-3p and miR-92a-3p were determined. Besides, human bronchial epithelial cells (16HBECs) were purchased, and they were treated by varying concentrations of cigarette smoke extract (CSE). The 16HBECs were, additionally, transfected by miR-221-3p mimic, miR-92a-3p mimic, miR-221-3p inhibitor or miR-92a-3p inhibitor, and cytokines released by them, including TNF-α, IL-8, IL-1β, and TGF-β1, were monitored using enzyme linked immunosorbent assay (ELISA) kits.

Results: Chronic obstructive pulmonary disease patients possessed higher serum levels of miR-221-3p and miR-92a-3p than healthy volunteers (p < 0.05), and both miR-221-3p and miR-92a-3p were effective biomarkers in diagnosing stable COPD from acute exacerbation COPD. Moreover, viability of 16HBECs was undermined by CSE treatment (p < 0.05), and exposure to CSE facilitated 16HBECs' release of TNF-α, IL-8, IL-1β, and TGF-β1 (p < 0.05). Furthermore, miR-221-3p/miR-92a-3p expression in 16HBECs was significantly suppressed after transfection of miR-221-3p/miR-92a-3p inhibitor (p < 0.05), which abated CSE-triggered increase in cytokine production and decline in viability of 16HBECs (p < 0.05).

Conclusion: MiR-221-3p and miR-92a-3p were involved in CSE-induced hyperinflammation of COPD, suggesting that they were favorable alternatives in diagnosing COPD patients with smoking history.

Keywords: chronic obstructive pulmonary disease; cigarette smoke extract; diagnosis; inflammation; miR-221-3p; miR-92a-3p.

MeSH terms

  • Aged
  • Airway Remodeling / genetics
  • Apoptosis / genetics
  • Bronchi / pathology
  • Case-Control Studies
  • Cell Line
  • Cell Proliferation / genetics
  • Cell Survival / genetics
  • Cytokines / metabolism
  • Epithelial Cells / metabolism
  • Female
  • Genetic Association Studies
  • Genetic Predisposition to Disease
  • Humans
  • Inflammation / genetics*
  • Male
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / genetics*
  • Pulmonary Disease, Chronic Obstructive / pathology
  • Pulmonary Disease, Chronic Obstructive / physiopathology
  • Smoking / genetics*

Substances

  • Cytokines
  • MIRN221 microRNA, human
  • MIRN92 microRNA, human
  • MicroRNAs