Study highlights microRNA differences between patients with HeFH and HoFH
A new study identified specific microRNAs (miRNAs) and their target genes associated with the severity of familial hypercholesterolemia (FH). The findings reveal distinct miRNA expression patterns in patients with heterozygous FH (HeFH) and homozygous FH (HoFH) compared to healthy individuals, highlighting their roles in cholesterol metabolism and cardiovascular disease.
The researchers utilized bioinformatics tools to examine microarray data, uncovering crucial miRNAs and their target genes associated with FH and its severity. They compared the differentially expressed serum miRNAs among healthy individuals, patients with HeFH, and patients with HoFH. The target genes were analyzed in silico, with gene ontology (GO) enrichment conducted via Cytoscape, and protein-protein interaction and co-expression networks assessed using the STRING and GeneMANIA plugins.
The analysis showed that certain miRNAs, including hsa-miR-604, hsa-miR-652-5p, and hsa-miR-4451, were more highly expressed in patients with FH compared to healthy individuals. Conversely, miRNAs such as hsa-miR-3140-3p, hsa-miR-550a-5p, and hsa-miR-363-3p were less expressed. Patients with HeFH had higher levels of miRNAs like hsa-miR-1183, hsa-miR-1185-1-3p, hsa-miR-122-5p, hsa-miR-19a-3p, hsa-miR-345-3p, and hsa-miR-34c-5p than both patients with HoFH and healthy subjects. Increased miRNA expression affected genes involved in heart muscle development, cholesterol production, RNA editing for apolipoprotein B, and LDL-cholesterol levels. Reduced miRNA expression influenced genes associated with coronary artery disease markers, lipid metabolism, cell adhesion and migration, type 2 diabetes, and cholesterol metabolism. Key genes were enriched in processes related to biological regulation, intracellular nucleic acid binding, and the TGF-β signaling pathway.
Reference
Cione E, Mahjoubin-Tehran M, Bacchetti T, et al. Profiling of differentially expressed MicroRNAs in familial hypercholesterolemia via direct hybridization. Noncoding RNA Res. 2024;9(3):796-810. doi: 10.1016/j.ncrna.2024.02.017. PMID: 38590435; PMCID: PMC10999490.
