MiR-3202 protects smokers from chronic obstructive pulmonary disease through inhibiting FAIM2: An in vivo and in vitro study.

Abstract

Previous study found the variable miR-3202 as a potential biomarker in smoker with or without chronic obstructive pulmonary disease (COPD). This study aims to identify the molecular involvement of miR-3202 in the pathophysiology of COPD. Level of miR-3202 in blood sample of non-smoker non-COPD(C), smoker without COPD(S), smoker with stable COPD(S-COPD) and smoker with acute exacerbation COPD(AE-COPD) was observed by quantitative real-time PCR. By bioinformatics prediction, Fas apoptotic inhibitory molecule 2 (FAIM2) was identified as a potential target of miR-3202. In vitro, human bronchial epithelial (HBE) cells and cigarette smoke extract (CSE) stimulated T lymphocytes were co-cultured. Cell proliferation and apoptosis of HBE cells were determinated. In vivo, rats were exposed in cigarette smoke for 30 days and expression of miR-3202 and FAIM2 in bronchia were detected. Results showed that The miR-3202 was down-regulated in S, S-COPD and AE-COPD group when compared with C group. Decreased level of miR-3202 was also observed in CSE treated T lymphocyte. Additionally, CSE stimulation increased INF-γ and TNF-α levels and FAIM2 expression whereas inhibited Fas and FasL expressions in T lymphocytes. However, these effects were significantly suppressed by miR-3202 overexpression and enhanced by miR-3202 inhibitor. Likely to exogenous miR-3202, FAIM2 knockdown significantly inhibited HBE cells apoptosis, as well as inhibited INF-γ and TNF-α levels. In COPD rats model, miR-3202 was reduced while FAIM2 was up-regulated accordingly. Here, results suggest that high level miR-3202 in T lymphocytes may protect epithelial cells through targeting FAIM2. MiR-3202 might be used as a notable biomarker of COPD.

• Authors: Wen Shen, Jia Liu, Minjuan Fan, Shukun Wang, Yang Zhang, Linqiao Wen, Ruili Wang, Wei Wei, Na Li, You Zhang, Guohou Zhao
• Journal: Experimental cell research (Exp Cell Res) Vol. 362 Issue 2 Pg. 370-377 (01 15 2018) ISSN: 1090-2422 [Electronic] United States
• PMID: 29208459 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2017 Elsevier Inc. All rights reserved.

Chemical References

• Apoptosis Regulatory Proteins
• FAIM2 protein, human
• MIRN3202 microRNA, human
• Membrane Proteins
• MicroRNAs
• Protective Agents
• Tumor Necrosis Factor-alpha

Topics

• Animals
• Apoptosis (genetics)
• Apoptosis Regulatory Proteins (genetics)
• Bronchi (cytology, metabolism)
• Cell Proliferation (drug effects)
• Cells, Cultured
• Cigarette Smoking (metabolism)
• Coculture Techniques
• Epithelial Cells (chemistry, metabolism)
• Gene Expression (drug effects)
• Humans
• Membrane Proteins (genetics)
• MicroRNAs (blood, genetics)
• Protective Agents (chemistry, metabolism)
• Pulmonary Disease, Chronic Obstructive (genetics, metabolism, pathology)
• Rats
• Smokers
• T-Lymphocytes (chemistry, metabolism)
• Tumor Necrosis Factor-alpha (genetics)