Identifying common signatures and potential therapeutic biomarkers in COPD and lung cancer using miRNA-mRNA co-expression networks

Abstract

The association between non-small cell lung cancer (NSCLC) and chronic obstructive pulmonary disease (COPD) is now well established, as people with COPD are more likely to develop lung carcinoma. However, the evidence for this relationship is inconclusive and there is currently little information on the underlying molecular mechanisms. MicroRNAs (miRNAs) are one of the regulatory factors in NSCLC and COPD that their functions are widely studied in many chronic diseases and cancers. In this study, we applied systems biology approaches to identify and predict miRNAs that potentially play regulatory roles between COPD and NSCLC. We performed differential expression analysis on public miRNA and mRNA expression datasets, for both of diseases, and then we reconstructed two miRNA-mRNA co-expression networks and merged these two co-expression networks into a community co-expression network. Results indicated the existence of very common miRNAs (ex. hsa-miR-326 and hsa-miR-1293) and mRNAs (such as FAT2, ALOX5AP, and LDB2) between the two mentioned diseases. Moreover, we discovered specific miRNAs (hsa-miR-574-3p) that targeted common mRNAs. We utilized drug-target interaction networks to identify candidate drugs for common mRNAs, which can be considered in the treatment of two diseases (e.g. iloperidone). Generally, our study highlighted common miRNAs between COPD and NSCLC that as new signatures or biomarkers for therapeutic purposes. Investigating the miRNA biomarkers in this study improves our understanding about the shared mechanisms between COPD and NSCLC.

Keywords

• COPD
• Non-small cell lung cancer
• miRNA-mRNA network
• Co-expression networks
• Community networks