Abstrait

Prediction of circulating miRNAs and their target genes involved in venous thrombo-embolism (VTE) pathogenesis: A computational approach.

Srivastava S, Garg I, Ganju L, Kumar B

Venous thromboembolism (VTE) encompasses two clinically interrelated conditions; deep vein thrombosis (DVT) and pulmonary embolism (PE), the later one being potentially fatal. It is complex multifactorial disease which requires comprehensive understanding at molecular level. Currently, D-dimer is being clinically used for VTE diagnosis; however it has low specificity and diagnostic value. Till date, various experimental reports have discussed the functional role of microRNAs (miRNAs) in cardiovascular diseases, cancer, inflammation, atherosclerosis etc. Several recent studies have illustrated differential expression of various circulating miRNAs and their potential diagnostic and therapeutic values for VTE patients. These small RNAs are noncoding and suppress their gene targets at the post-transcriptional level. In the present study, we systematically evaluated available researches and performed bio-informatics analysis to provide new insights into the role of miRNA in VTE pathophysiology. Purpose of study: The aim of the present study was to consolidate the current information available on miRNAs linked to venous thrombosis and to identify the most potent miRNA and its target genes which could be useful in designing the future therapeutic strategies for treatment of venous thrombosis. Method: In the present study we retrieved recent articles associating various miRNAs with VTE pathophysiology. The eligibility criteria for inclusion in this study was met by six articles which pointed towards sixteen different miRNAs linked with VTE susceptibility. We further listed out their target genes using online miRNA target prediction tools and subjected each of them to functional gene enrichment analysis and pathway analysis. Results: Eleven functionally relevant miRNAs were identified after pathway analysis which regulate target genes involved in VTE associated pathways, such as hemostasis, blood coagulation, platelet activation, endothelin signalling and angiogenesis pathways. Other five miRNAs did not show any target genes in blood coagulation pathway and platelet activation, hence they were not considered for downstream analysis. The selected list of miRNAs was subjected to network analysis. Conclusions: Our in silico analysis results pointed towards four most potential miRNAs that could be used as biomarkers of VTE; hsa-mir-320a, hsa-mir-195, hsa-mir-103a-3p, hsa-mir- 26a. These miRNAs could also prove as critical targets for understanding molecular regulatory mechanism underlying pathophysiology and therapeutic interventions during VTE treatment. This analysis advance our understanding of regulatory mechanism of genes involved in VTE. Further in vivo validation of this data is required for confirming the present observation.