Studying the system-level involvement of microRNAs in Parkinson's disease

Parkinson's Disease (PD) is a progressive neurologic disorder that affects movement and balance. Recent studies have revealed the importance of microRNA (miR) in PD. However, the detailed role of miR and its regulation by Transcription Factor (TF) remain unexplored. In this work for the first time we have studied TF-miR-mRNA regulatory network as well as miR co-expression network in PD.

We compared the 204 differentially expressed miRs from microarray data with 73 PD related miRs obtained from literature, Human MicroRNA Disease Database and found a significant overlap of 47 PD related miRs (p-value<0.05). Functional enrichment analyses of these 47 common (Group1) miRs and the remaining 157 (Group2) miRs revealed similar kinds of over-representative GO Biological Processes and KEGG pathways. This strengthens the possibility that some of the Group 2 miRs can have functional roles in PD progression, hitherto unidentified in any study. In order to explore the cross talk between TF, miR and target mRNA, regulatory networks were constructed. Study of these networks resulted in 14 Inter-Regulatory hub miRs whereas miR co-expression network revealed 18 co-expressed hub miRs. Of these 32 hub miRs, 23 miRs were previously unidentified with respect to their association with PD. Hierarchical clustering analysis further strengthens the roles of these novel miRs in different PD pathways. Furthermore hsa-miR-92a appeared as novel hub miR in both regulatory and co-expression network indicating its strong functional role in PD. High conservation patterns were observed for most of these 23 novel hub miRs across different species including human. Thus these 23 novel hub miRs can be considered as potential biomarkers for PD.

Our study identified 23 novel miR markers which can open up new avenues for future studies and shed lights on potential therapeutic targets for PD.