Meta-analysis of long non-coding RNA expression profile in Parkinson's disease

Parkinson's disease (PD) pathogenesis involves dopaminergic neuron loss, yet the role of long non-coding RNAs (lncRNAs) remains poorly characterized. In this study, we perform a comprehensive meta-analysis of PD transcriptomes, identifying the top 50 significantly dysregulated lncRNAs (25 upregulated including NEAT1 and LINC00869; 25 downregulated including CASC2 and HULC) from 718 differentially expressed lncRNAs. Through functional enrichment analyses, we demonstrate that upregulated lncRNAs predominantly regulate neuroinflammatory pathways (NEAT1-NF-κB), α-synuclein aggregation (HOTAIR), regulation of gene expression epigenetic (MEG3) and vesicle trafficking (LINC00869), while downregulated lncRNAs control apoptotic signaling (CASC2-MAPK), lysosomal function (SFTA3), and metabolic homeostasis (HULC). Additionally, the KEGG pathway analysis convergence of ATXN8OS with spinocerebellar ataxia pathways further highlighted shared mechanisms of neurodegeneration. Notably, lncRNA-protein interaction network analysis of PD-associated lncRNAs identified two distinct interactomes: (1) an upregulated module (10 hubs/50 proteins/360 edges) enriched for neuroinflammation (NEAT1-centric), and (2) a downregulated module (8 hubs/190 proteins/1,282 edges) dominated by apoptotic regulation (CASC2-centric). These findings provide a systemic proof that lncRNAs networks may serve as diagnostic biomarkers and therapeutic targets.