Plasma exosome-derived microRNAs expression profiling and bioinformatics analysis under cross-talk between increased low-density lipoprotein cholesterol level and ATP-sensitive potassium channels variant rs1799858

Abstract

Background: Exosome-derived microRNAs (exo-miRs) as messengers play important roles, in the cross-talk between genetic [ATP-sensitive potassium channels (KATP) genetic variant rs1799858] and environmental [elevated serum low-density lipoprotein cholesterol (LDL-C) level] factors, but the plasma exo-miRs expression profile and its role in biological processes from genotype to phenotype remain unclear. Methods: A total of 14 subjects with increased LDL-C serum levels (≥ 1.8 mmol/L) were enrolled in the study. The KATP rs1799858 was genotyped by the Sequenom MassARRAY system. The plasma exo-miRs expression profile was identified by next-generation sequencing. Results: 64 exo-miRs were significantly differentially expressed (DE), among which 44 exo-miRs were up-regulated and 20 exo-miRs were down-regulated in those subjects carrying T-allele (TT + CT) of rs1799858 compared to those carrying CC genotype. The top 20 up-regulated DE-exo-miRs were miR-378 family, miR-320 family, miR-208 family, miR-483-5p, miR-22-3p, miR-490-3p, miR-6515-5p, miR-31-5p, miR-210-3p, miR-17-3p, miR-6807-5p, miR-497-5p, miR-33a-5p, miR-3611 and miR-126-5p. The top 20 down-regulated DE-exo-miRs were let-7 family, miR-221/222 family, miR-619-5p, miR-6780a-5p, miR-641, miR-200a-5p, miR-581, miR-605-3p, miR-548ar-3p, miR-135a-3p, miR-451b, miR-509-3-5p, miR-4664-3p and miR-224-5p. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were subsequently implemented to identify the top 10 DE-exo-miRs related specific target genes and signaling pathways. Only 5 DE-exo-miRs were validated by qRT-PCR as follows: miR-31-5p, miR-378d, miR-619-5p, miR-320a-3p and let-7a-5p (all P < 0.05). Conclusion: These results firstly indicated the plasma exo-miRs expression profile bridging the link between genotype (KATP rs1799858) and phenotype (higher LDL-C serum level), these 5 DE-exo-miRs may be potential target intermediates for molecular intervention points.