Comprehensive Analysis of miRNA-mRNA-lncRNA Networks in Non-Smoking and Smoking Patients with Chronic Obstructive Pulmonary Disease

Cell Physiol Biochem. 2018;50(3):1140-1153. doi: 10.1159/000494541. Epub 2018 Oct 24.

Abstract

Background/aims: Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. This study aimed to identify overlapping or diverging dysregulated genes, lncRNAs, miRNAs and signaling pathways in smoking and non-smoking chronic obstructive pulmonary disease (COPD).

Methods: Compared to normal controls, we identified the shared and divergent differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in smoking and non-smoking COPD by RNA-sequencing and bioinformatics analysis. Functional annotation of DEmRNAs were performed. Both cis and trans-target DEmRNAs of DElncRNAs were identified. The target DEmRNAs of DEmiRNAs were identified as well. The DEmiRNA-DEmRNA-DElncRNA interaction network was constructed. QRT-PCR was performed to validat the selected DEmiRNAs, DEmRNA and DElncRNAs in COPD.

Results: Compared to normal control, 1234 DEmRNAs, 96 DElncRNAs and 151 DEmiRNAs were identified in non-smoking patients with COPD; 670 DEmRNAs, 44 DElncRNAs and 63 DEmiRNAs were identified in smoking patients with COPD. Leukocyte transendothelial migration and pathways in cancer were significantly enriched pathways in non-smoking and smoking COPD, respectively. MiR-122-5p-A2M-LINC00987/A2M-AS1/ linc0061 interactions might play key roles in COPD irrespective with the smoking status. Let-7-ADRB1-HLA-DQB1-AS1 might play a key role in the pathogenesis of smoking COPD while miR-218-5p/miR15a-RORA-LOC101928100/LINC00861 and miR-218-5p/miR15a-TGFβ3-RORA-AS1 interactions might involve with non-smoking COPD.

Conclusion: We identified the shared and diverging genes, lncRNAs, miRNAs and their interactions and pathways in smoking and non-smoking COPD which provided clues for understanding the mechanism and developing novel diagnostic and therapeutic strategies for COPD.

Keywords: Chronic Obstructive Pulmonary Disease (COPD); genes; lncRNAs; miRNAs; smoking.

Publication types

  • Comparative Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Computational Biology
  • Female
  • Gene Expression Regulation
  • Gene Regulatory Networks / genetics
  • Humans
  • Male
  • MicroRNAs / metabolism*
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / metabolism
  • Pulmonary Disease, Chronic Obstructive / pathology*
  • RNA, Long Noncoding / metabolism*
  • RNA, Messenger / metabolism*
  • Smoking*

Substances

  • MicroRNAs
  • RNA, Long Noncoding
  • RNA, Messenger