Abstract
The involvement of genes and miRNAs in the development of atherosclerosis is a challenging problem discussed in recent publications. It is necessary to establish which miRNAs affect the expression of candidate genes. We used known candidate atherosclerosis genes to predict associations. The quantitative characteristics of interactions of miRNAs with mRNA candidate genes were determined using the program, which identifies the localization of miRNA binding sites in mRNA, the free energy interaction of miRNA with mRNA. In mRNAs of GAS6 and NFE2L2 candidate genes, binding sites of 21 miRNAs and of 15 miRNAs, respectively, were identified. In IRS2 mRNA binding sites of 25 miRNAs were located in a cluster of 41 nt. In ADRB3, CD36, FASLG, FLT1, PLA2G7, and PPARGC1A mRNAs, clusters of miR-466, ID00436.3p-miR, and ID01030.3p-miR BS were identified. The organization of overlapping miRNA binding sites in clusters led to their compaction and caused competition among the miRNAs. The binding of 53 miRNAs to the mRNAs of 14 candidate genes with free energy interactions greater than −130 kJ/mole was determined. The miR-619-5p was fully complementary to ADAM17 and CD36 mRNAs, ID01593.5p-miR to ANGPTL4 mRNA, ID01935.5p-miR to NFE2L2, and miR-5096 to IL18 mRNA. Associations of miRNAs and candidate atherosclerosis genes are proposed for the early diagnosis of this disease.
Highlights
The diagnosis, prevention and treatment of atherosclerosis are important tasks of modern medicine (Byrne et al, 2014; Churov et al, 2019; Solly et al, 2019; Shoeibi, 2020)
It was found that the binding site (BS) of some miRNAs formed clusters in the 5 -untranslated regions (5 UTR) and coding sequence (CDS) sequences of mRNA, resulting in competition between these miRNAs for binding to mRNA and, for suppressing the expression of the target gene
The revealed associations of several miRNAs that bind to mRNAs of different candidate genes make it possible to predict the effect of these miRNAs on the corresponding genes, which can be expressed to different degrees
Summary
The diagnosis, prevention and treatment of atherosclerosis are important tasks of modern medicine (Byrne et al, 2014; Churov et al, 2019; Solly et al, 2019; Shoeibi, 2020). As a result of a review of various publications, it seems that the approaches used to search for markers for the diagnosis and treatment of atherosclerosis, including miRNA, have not yet solved the problem of diagnosing and treating atherosclerosis (Chen et al, 2020; Li et al, 2020; Ryu et al, 2020; Sun et al, 2020; Wang W. et al, 2020; You et al, 2020) In human, it is known about 7000 miRNA and more than 20,000 genes, and it is unknown how many miRNA and genes from them participate in the development of atherosclerosis miRNA Interactions With Candidate Atherosclerosis Genes (Byrne et al, 2014; Toba et al, 2014; Lu et al, 2018; Liu et al, 2020; Shi et al, 2020). We discuss what should be taken into consideration when reviewing the problem of miRNA interaction with candidate genes and show the need to use a systematic approach in establishing the most probable associations of miRNA and target genes
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