Identification of the Major miRNAs, Target Genes and Signaling Pathways Associated with Milk Production Using miRNA-Seq

miRNA molecules are short sequences (With an average length of 22 nucleotides) that regulate many biological processes by suppressing gene expression. Milk production is a physiological process that influence by a large number of genes, miRNAs and signaling pathways. In this study, identification of miRNAs, their target genes and signaling pathways were done by investigation of interspecies conserved miRNAs in mouse, cattle and goat.
In this study, to investigate molecular mechanism of miRNA’s effect on milk production, firstly data were downloaded with accession number GSM1295115 for mouse species, GSM1295118 for cattle species and GSM969927 for goat species from GEO database. Identification of miRNAs was done by mirDeep2. In this study, mirwalk database was used to detect target genes of miRNA which expressed in all three species. The mirwalk database is also able to estimates target genes based on the ten other databases’ algorithms. Visualization of miRNA and their target genes’ interaction was performed by cytoscape. DAVID database was used to study target genes-related gene and signaling pathways.
According to these results miR-93-5p, miR-27b-3p, miR-27a-3p and miR-200c-3p genes are the most important miRNA and Pten, Rlim, Pdik1l and Setd5 genes are the most important target genes on the process of milk production and pathways of milk components biosynthesis. One of the most important results of this study was detected Setd5 as the novel milk production process-related gene. Gene pathway analysis showed Focal adhesion pathway, MAPK signaling pathway, mTOR signaling pathway, PI3K-Akt signaling pathway and Neurotrophin signaling pathway were the most important of gene pathways which active by target genes and have a vital role in milk production biosynthesis and development of mammary glands. Theses gene pathways could effect on milk production physiologically and biologically by influencing on the development of alveolar cells, increasing branches, developing of mammary tissue, amino acid metabolism, influencing on endocrine system, prolactin signaling pathway and influencing on the milk compounds synthesis such as fat, protein and lactose.
According to critical role of the important miRNA in the studied network and target genes of these molecules and also investigated gene pathways, it could be used in breeding programs as the most important regulators in milk production process. This information could be used to introduce and apply candidate genes for the gene assisted selection method or genomic selection. Given that milk production is along with development and differentiation of breast tissue, miRNA molecules and target genes which investigate in this study could be the good candidates in all developmental and differential processes.