Background
Different factors have been introduced which influence the pathogenesis of chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC). COPD as an independent factor is involved in the development of lung cancer. Moreover, there are certain resemblances between NSCLC and COPD, such as growth factors, activation of intracellular pathways, as well as epigenetic factors. One of the best approaches to understand the possible shared pathogenesis routes between COPD and NSCLC is to study the biological pathways that are activated. MicroRNAs (miRNAs) are critical biomolecules that implicate the regulation of several biological and cellular processes. As such, the main goal of this study was to use a systems biology approach to discover common dysregulated miRNAs between COPD and NSCLC, one that targets most genes within common enriched pathways.
Results
To reconstruct the miRNA-pathways for each disease, we used the microarray miRNA expression data. Then, we employed “miRNA set enrichment analysis” (MiRSEA) to identify the most significant joint miRNAs between COPD and NSCLC based on the enrichment scores. Overall, our study revealed the involvement of the targets of miRNAs (such as has-miR-15b, hsa-miR-106a, has-miR-17, has-miR-103, and has-miR-107) in the most important common biological pathways.
Conclusions
According to the promising results of the pathway analysis, the identified miRNAs can be utilized as the new potential signatures for therapy through understanding the molecular mechanisms of both diseases.
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.
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