Comparison of COPD and Lung Cancer Mechanisms for Identifying MicroRNA Biomarkers By The Reconstruction of miRNA-mRNA Co-Expression Network

Abstract

Background: The association between lung cancer 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 lung cancer and COPD that their functions are widely studied in many chronic diseases and cancers. Rationally, determining common miRNAs for both of diseases could provide a more detailed picture of this association and the involved molecular mechanisms. In this study, we applied systems biology approaches to identify and predict miRNAs that potentially play regulatory roles between COPD and lung cancer. Results: We performed differential expression analysis on public miRNA and mRNA expression data sets, for both of diseases, and calculated two correlation matrices between miRNA and mRNA for case and control samples. Then we constructed 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 (e.g. iloperidone) for common mRNAs that could be considered in treatment both of diseases.Conclusions: Generally, our study highlighted common miRNAs between COPD and lung cancer that could be used as new signatures or biomarkers for therapeutic purposes. Moreover, discovered candidate drugs may be applied in the treatment of both mentioned diseases. Investigating the miRNA biomarkers in this study improves our understanding about the shared mechanisms between COPD and lung cancer.