Effect Of SO₂ On MicroRNA Expression Profile Of Human Vascular Smooth Muscle Cells

Sulfur dioxide?SO₂?is a toxic gas and one of the major air pollutants,which is mainly derived from the combustion of industrial fuels.Epidemiological studies have shown that exposure to SO₂ is associated with cardiovascular disease.Cardiovascular diseases such as hypertension,coronary artery disease,atherosclerosis and congestive heart failure are the leading causes of death worldwide.According to the World Health Organization,approximately 17.9 million people died of cardiovascular disease in 2016,accounting for all deaths 31%.Micro RNAs?mi RNA,mi R?are a class of small-molecule endogenous non-coding RNAs that interact with the target m RNA's 3?UTR sequence to mediate the degradation or translation of the target m RNA and exert gene regulation.It is estimated that mi RNAs can mediate more than 30% of the human genome and play an important role in various biological processes of cells and the occurrence and development of multiple diseases.However,it is not clear whether mi RNAs are involved in cardiovascular disease caused by SO₂.In this study,mi RNA high-throughput sequencing technology and RT-PCR technology were used to screen and verify differentially expressed mi RNAs in human aortic vascular smooth muscle cells exposed to SO₂.A total of 106 differentially expressed mi RNAs were detected,of which 67 were up-regulated and 39 were up-regulated.Combined with the literature and sequencing results,five mi RNAs?hsa-mir-548 ba,hsa-mir-3152-5p,hsa-mir-466,hsa-mir-605-3p,hsa-mir-10523-5p?that may be related to cardiovascular diseases were randomly selected for RT-PCR validation,and the validation results were consistent with the sequencing results.Bioinformatics analysis was used to predict the target genes of differentially expressed mi RNAs and to enrich the target genes with Gene Oncology?GO?functional enrichment and Kyoto Encyclopedia of Genes and Genomes?KEGG?Pathway enrichment.The results showed that there were 17423 target genes,200594 Target sites.A large number of target genes are enrichedin cells and are mainly involved in the regulation of development and metabolic processes;target genes are mainly concentrated in cysteine and methionine metabolism,cancer,endocrine and other factors regulating calcium reabsorption,inositol phosphate metabolism,TGF-beta signaling pathway,etc.,many of them are involved in the development of cardiovascular disease.The key mi RNA hsa-mi R-10b-3p was selected and the target gene protein phosphatase 3 catalytic subunit?PPP3CC?was selected through literature review and bioinformatics analysis.The target relationship between hsa-mir-10b-3p and PPP3 CC was verified by double luciferase reporter gene,which provided the basis for enriching the mi RNA and target gene library related to cardiovascular diseases and studying the pathogenesis of cardiovascular diseases induced by SO₂.This study will have a positive significance for the early diagnosis,pathogenesis,potential targets and innovative drug development of cardiovascular diseases induced by SO₂ and other air pollutants,and provide a new way and theoretical basis for the prevention of the induction of cardiovascular diseases induced by air pollutants.