Novel role of microRNA146b in promoting mammary alveolar progenitor cell maintenance

Abstract

Here, we have shown that miR146b promotes the maintenance of pregnancy derived mammary luminal alveolar progenitors. MiR146b expression was significantly higher in the mammary glands of pregnant and lactating mice compared to virgin. Furthermore, miR146b levels were significantly higher in the mouse mammary glands exposed to sex hormones, estrogen plus progesterone compared to untreated control animals. Pregnancy derived primary mouse mammary epithelial cells, knocked down of miR146b showed a significant reduction in the number of hollow acinar organoid structures formed on 3D Matrigel and in β-casein expression. This demonstrates that miR146b promotes the maintenance of pregnancy derived mammary luminal alveolar progenitors. It has been shown that mouse mammary luminal progenitors give rise to hollow organoid structures while solid organoid structure are derived from stem cells. Among several of miR146b targets, miR146b knockdown resulted in preferential STAT3β overexpression. In the primary mouse mammary epithelial cells, overexpression of STAT3β isoform caused mammary epithelial cells death and a significant reduction in β-casein mRNA expression. Therefore, we conclude that, during pregnancy, miR146b is involved in luminal alveolar progenitor cell maintenance by, at least partially, regulating STAT3β.