In silico Prediction of miRNA Interactions With Candidate Atherosclerosis Gene mRNAs.

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.

In silico prediction of human genes as potential targets for rice miRNAs.

BACKGROUND: Exogenous microRNAs (miRNAs) enter the human body through food, and their effects on metabolic processes can be considerable. It is important to determine which miRNAs from plants affect the expression of human genes and the extent of their influence. METHOD: The binding sites of 738Oryza sativa miRNAs (osa-miRNAs) that interact with 17 508 mRNAs of human genes were determined using the MirTarget program. RESULT: The characteristics of the binding of 46 single osa-miRNAs to 86 mRNAs of human genes with a value of free energy (ΔG) interaction equal 94%-100% from maximum ΔG were established. The findings showed that osa-miR2102-5p, osa-miR5075-3p, osa-miR2097-5p, osa-miR2919 targeted the largest number of genes at 38, 36, 23, 19 sites, respectively. mRNAs of 86 human genes were identified as targets for 93 osa-miRNAs of all family osa-miRNAs with ΔG values equal 94%-98% from maximum ΔG. Each miRNA of the osa-miR156-5p, osa-miR164-5p, osa-miR168-5p, osa-miR395-3p, osa-miR396-3p, osa-miR396-5p, osa-miR444-3p, osa-miR529-3p, osa-miR1846-3p, osa-miR2907-3p families had binding sites in mRNAs of several human target genes. The binding sites of osa-miRNAs in mRNAs of the target genes for each family of osa-miRNAs were conserved when compared to flanking nucleotide sequences. CONCLUSION: Target mRNA human genes of osa-miRNAs are also candidate genes of cancer, cardiovascular and neurodegenerative diseases.

Prediction of miRNA interaction with mRNA of stroke candidate genes.

BACKGROUND: The role of miRNA in tissue affected by stroke is actively studied, but it remains unclear which miRNAs and target genes are involved in the development of stroke. METHODS: The MirTarget program defines the following features of a miRNA binding to a mRNA: the binding start site, the location of the binding site in mRNA, the free energy of a miRNA binding with a mRNA, and the interaction schemes of miRNA and mRNA. RESULTS: The interaction of 6565 miRNAs with mRNAs of stroke candidate genes was determined. The association of the mRNAs of stroke candidate genes with miRNAs depends on the level of gene expression. Some highly expressed candidate genes are targets of miR-619-5p and miR-5095, which have binding sites located on overlapping mRNA nucleotide sequences (clusters). miR-619-5p and miR-5095 bind to mRNA of 15 genes. Clusters for the binding of miR-1273f,d,e are in mRNAs of highly expressed genes. The start sites of miR-1273d and miR-1273e binding in all clusters are in sequences with one and ten nucleotides, respectively. The clusters of multiple miR-574-5p and ID00470.5p-miR binding sites and the clusters of the miR-466, ID01030.3p-miR, and ID00436.3p-miR binding sites are in mRNAs of some genes expressed at low levels. CONCLUSION: The organization of miRNA binding sites into clusters reduces the length of mRNA and creates competition between miRNAs for binding to mRNA of a target gene. The characteristics of miRNA associations with target genes can be used to recommend markers for a diagnosis of stroke.

Prediction of clusters of miRNA binding sites in mRNA candidate genes of breast cancer subtypes.

The development of breast cancer (BC) subtypes is controlled by distinct sets of candidate genes, and the expression of these genes is regulated by the binding of their mRNAs with miRNAs. Predicting miRNA associations and target genes is thus essential when studying breast cancer. The MirTarget program identifies the initiation of miRNA binding to mRNA, the localization of miRNA binding sites in mRNA regions, and the free energy from the binding of all miRNA nucleotides with mRNA. Candidate gene mRNAs have clusters (miRNA binding sites with overlapping nucleotide sequences). mRNAs of EPOR, MAZ and NISCH candidate genes of the HER2 subtype have clusters, and there are four clusters in mRNAs of MAZ, BRCA2 and CDK6 genes. Candidate genes of the triple-negative subtype are targets for multiple miRNAs. There are 11 sites in CBL mRNA, five sites in MMP2 mRNA, and RAB5A mRNA contains two clusters in each of the three sites. In SFN mRNA, there are two clusters in three sites, and one cluster in 21 sites. Candidate genes of luminal A and B subtypes are targets for miRNAs: there are 21 sites in FOXA1 mRNA and 15 sites in HMGA2 mRNA. There are clusters of five sites in mRNAs of ITGB1 and SOX4 genes. Clusters of eight sites and 10 sites are identified in mRNAs of SMAD3 and TGFB1 genes, respectively. Organizing miRNA binding sites into clusters reduces the proportion of nucleotide binding sites in mRNAs. This overlapping of miRNA binding sites creates a competition among miRNAs for a binding site. From 6,272 miRNAs studied, only 29 miRNAs from miRBase and 88 novel miRNAs had binding sites in clusters of target gene mRNA in breast cancer. We propose using associations of miRNAs and their target genes as markers in breast cancer subtype diagnosis.