Two way network construction and analysis of mRNA, miRNA and lncRNA reveals critical regulators and regulatory modules in cardiovascular diseases.

BACKGROUND

Cardiovascular diseases contribute to the leading cause of deaths (31%) in the world population.

OBJECTIVE

The objective of this study is to compile non-coding RNA-gene interaction into a core regulatory network whose dysregulation might play an important role in disease progression.

METHOD

We applied a structured approach to reconstruct the interaction network of lncRNAs, miRNAs and genes involved in cardiovascular diseases. For network construction, we used 'diseasome to interactome' and 'interactome to diseasome' approaches and developed two regulatory networks in heart disorders. In diseasome to interactome approach, starting from a disease-centric network we, expanded the data into an interaction network. However in interactome to diseasome, we used a set of guide genes, miRNAs and lncRNAs to arrive at the common diseases. The disease-centric network in combination with the interaction network will shed light on the interconnected components in a huge diseasome network implicated in heart disorders and manifested through small sub-networks while progressing. Using the above networks we created a sub-networks consisting only of hub genes, miRNAs and lncRNAs on both approaches. The dysregulation of any one of the hubs can lead to a disease condition.

RESULTS

The top ranking hubs common in both the sub-networks were found to be VEGFA, MALAT1, HOTAIR, H19 and hsa-miR-15a. Our network based study reveals an entanglement of regulatory sub-network of miRNAs, lncRNAs and genes in multiple conditions.

CONCLUSION

The identification of hubs in the core triple node network of elements in disease development and progression demonstrates a promising role for network based approaches in targeting critical molecules for drug development.