MicroRNA expression profile of cholesterol metabolism analysis mediated by Thelenota ananas desulfated holothurin A saponin in RAW264.7 macrophage-foam cells

Abstract

Saponins from the sea cucumber, Thelenota ananas, have been reported to modulate cholesterol metabolism and may be useful in treating atherosclerosis and related diseases, but the mechanism remains unclear. This study is designed to investigate the effect of the saponin desulfated holothurin A (desHA), prepared from Thelenota ananas, on cholesterol and lipid metabolism in oxidized low-density lipoprotein (oxLDL)-induced RAW264.7 macrophage-foam cells. The detection and prediction of miRNAs were conducted by high-throughput sequencing and associated bioinformatics analysis. We found that desHA could play an essential role in the species and expression of miRNAs. There were more abundant miRNAs in the desHA-treated groups. miR-365-2-5p, -125b-1-3p, -744-5p, -330-3p, -125a-3p and -3057-5p were extremely suppressed by desHA under the oxLDL treatment, while miR-212-3p and miR-132-3p were significantly upregulated by desHA. The clusters of orthologous groups (COG) analysis indicated that the detected miRNAs participated in lipid transport and metabolism (I) and secondary metabolite biosynthesis, transport, and catabolism (Q), which were closely linked with cholesterol metabolism. The network of the nine miRNAs with higher degree of differential expression (miR-125a-3p, -23b-5p, -3057-5p, -330-3p, -365-2-5p and -744-5p, -345-5p -212-3p and -132-3p) and their target genes further showed relationships with inflammatory response, cell proliferation and cholesterol metabolism. Due to miR-125a-3p and miR-365-2-5p being involved in the regulation of more genes, which are mostly related to the functions involved in cholesterol metabolism, they may be potential targets for desHA to prevent or treat atherosclerosis.