HIGH-RESOLUTION MAPPING OF REGULATORY RNA INTERACTIONS IN NEURODEGENERATIVE DISORDERS

Abstract

The regulatory function of regulatory RNAs such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) has become an important factor in regulating genes, and has been implicated in the pathogenesis of neurodegenerative disorders including Alzheimer disease and Parkinson disease. Nevertheless their interactions are too complicated to be described at a systems level. This paper set out to conduct high-resolution mapping of regulatory RNA interactions and build integrated RNA interaction networks to gain a clearer idea of how they contribute to the onset of neurodegenerative diseases. RNA sequencing datasets were standardized in bioinformatics pipelines and analyzed publicly available datasets. The analysis was done using differential expression to find important miRNAs, lncRNAs, and circRNAs. Predictive tools were used to establish interaction networks and competing endogenous RNA (ceRNA) networks were visualized. The analysis of functional enrichment was conducted (Gene ontology and KEGG pathway analysis) to determine related biological processes and pathways. The analysis revealed a number of differentially expressed regulatory RNAs and found complex interactions networks between key regulatory hubs. Enrichment analysis showed a strong engagement in neuronal apoptotic, synaptic signaling, and inflammatory responses pathways. A number of candidate RNAs were found as potential biomarkers that are associated with disease progression. This integrative methodology offers a holistic perspective of RNA regulatory networks in neurodegenerative diseases and identifies possible molecular hits to diagnose and treat.