Let-7g-5p regulates mouse mammary cells differentiation and function by targeting PRKCA

MicroRNAs (miRNAs) are closely related with the posttranscriptional regulation of gene expression. Our past study showed that let-7g-5p decreased during pregnancy and lactation in mouse mammary gland, what suggested the prospective regulating role of let-7g-5p in mammary epithelial cells. In this study, to unravel the role of let-7g-5p, we found PRKCA (PKC-alpha, PKC-α) might serve as potential targets of let-7g-5p by bioinformatics. Then let-7g-5p was knocked down by an antisense oligonucleotide in mouse primary mammary epithelial cells. As predicted, PRKCA gene expression and mammary epithelial cells growth were increased by anti-let-7g-5p regulation in vitro. By using reporter constructs, it showed that the let-7g-5p could direct binding with 3'-the untranslated regions (3'-UTR) of PRKCA mRNA. Furthermore, ectopic overexpression of let-7g-5p in vivo reduced PRKCA and β-casein protein expression as well as inhibited mammary gland growth. These results suggested that let-7g-5p could inhibit the mammary epithelial cells differentiation and β-casein protein synthesis and expression through suppression of PRKCA on the cycle of mammary cell differentiation and development and that let-7g-5p may be a novel important regulated target in mammary cells function.