Meta-analysis of differentially expressed non-coding RNA signatures (lncRNAs, miRNAs, and snoRNAs) in Parkinson's disease

Parkinson's disease (PD), the second most common neurodegenerative disorder globally, arises from dopaminergic neuron degeneration and Lewy body accumulation, with increasing evidence highlighting critical regulatory roles of non-coding RNAs (ncRNAs). Our comprehensive meta-analysis integrating four multi-omics datasets revealed 732 significantly dysregulated ncRNAs (294 upregulated, 439 downregulated), including key candidates like NEAT1, MIR182 and SNORA63 demonstrating strong diagnostic potential. Functional characterization identified distinct pathological networks: upregulated ncRNAs predominantly influenced nuclear organization (NEAT1), RNA processing (SNORA63) and cell cycle regulation (MIR133B), while downregulated species were enriched in vascular dysfunction (MIR-451A/MIR-182) and vesicular trafficking pathways (SFTA3). Notably, we discovered neuroprotective microRNA-mediated activation of oncogenic pathways (hsa05206; MIR133B, MIR18A, MIR451A clusters) concurrent with ATXN8OS-associated suppression of spinocerebellar ataxia pathways (hsa05020). Network analysis uncovered two divergent interactomes - a focused upregulated network (4 hubs/32 proteins/151 edges) versus an extensive downregulated network (5 hubs/245 proteins/2826 edges) - suggesting the latter's predominant role in PD progression. Our findings systematically decode ncRNA regulatory architecture in PD, delivering both mechanistic insights and clinically actionable targets for early diagnosis and therapeutic development.