Bioinformatics Analysis of Unique High-Density Lipoprotein-MicroRNAs Cargo Reveals Its Neurodegenerative Disease Potential

Recent findings have identified high-density lipoprotein (HDL) as a carrier of microRNAs, small non-coding RNAs that regulate gene expression, suggesting a potential novel functional and biochemical role for HDL-microRNA cargo. Here, we conduct an in-depth bioinformatics analysis of unique HDL-microRNA cargo to uncover their molecular mechanisms and potential applications as clinical biomarkers. First, using the Gene Expression Omnibus (GEO), we performed computational analysis on public human microRNA array datasets (GSE 25425; platform GPL11162) obtained from highly purified fractions of HDL in human plasma in order to identify their unique miRNA cargo. This led to the identification of eleven miRNAs present only in HDL, herein listed: hsa-miR-210, hsa-miR-26a-1, hsa-miR-628-3p, hsa-miR-31, hsa-miR-501-5p, hsa-miR-100-3p, hsa-miR-571, hsa-miR-100-5p, hsa-miR-23a, hsa-miR-550, and hsa-miR-432. Then, these unique miRNAs present in HDL were analyzed using a bioinformatics approach to recognize their validated target genes. The ClusterProfiler R package applied gene ontology and KEGG enrichment analysis. The key genes mainly enriched in the biological process of cellular regulation were identified and linked to neurodegeneration. Finally, the protein–protein interaction and co-expression network were analyzed using the STRING and GeneMANIA Cytoscape plugins.