Department of Molecular Cell Biology, Max Planck Institute of Biophysical Chemistry, Goettingen, Germany.
Nat Genet. 2010 Dec;42(12):1101-8. doi: 10.1038/ng.709. Epub 2010 Nov 7.
MicroRNAs are small noncoding RNAs that carry out post-transcriptional regulation of the expression of their target genes. However, their roles in mammalian organogenesis are only beginning to be understood. Here we show that the microRNA-212/132 family (which comprises miR-212 and miR-132) is indispensable during the development of the mammary glands in mice, particularly for the regulation of the outgrowth of the epithelial ducts. Mammary transplantation experiments revealed that the function of the miR-212/132 family is required in the stroma but not in the epithelia. Both miR-212 and miR-132 are expressed exclusively in mammary stroma and directly target the matrix metalloproteinase MMP-9. In glands that lack miR-212 and miR-132, MMP-9 expression increases and accumulates around the ducts. This may interfere with collagen deposition and lead to hyperactivation of the tumor growth factor-β signaling pathway, thereby impairing ductal outgrowth. Our results identify the miR-212/132 family as one of the main regulators of the epithelial-stromal interactions that are required for proper pubertal development of the mammary gland.
微小 RNA 是一类进行靶基因表达转录后调控的小非编码 RNA。然而，它们在哺乳动物器官发生中的作用才刚刚开始被理解。在这里，我们发现微小 RNA-212/132 家族（包含 miR-212 和 miR-132）在小鼠乳腺发育过程中是不可或缺的，特别是对于上皮导管的生长调控。乳腺移植实验表明，miR-212/132 家族的功能需要在基质中而不是在上皮中。miR-212 和 miR-132 都只在乳腺基质中表达，并直接靶向基质金属蛋白酶 MMP-9。在缺乏 miR-212 和 miR-132 的腺体中，MMP-9 的表达增加并在导管周围积聚。这可能会干扰胶原蛋白的沉积，并导致肿瘤生长因子-β信号通路的过度激活，从而损害导管的生长。我们的研究结果表明，miR-212/132 家族是调节上皮-基质相互作用的主要调控因子之一，这种相互作用对于乳腺的青春期正常发育是必需的。
