From the Shanghai Key Laboratory for Molecular Andrology, State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Shanghai 200031, China.
J Biol Chem. 2013 Oct 11;288(41):29369-81. doi: 10.1074/jbc.M113.454066. Epub 2013 Aug 19.
MicroRNAs are involved in a number of cellular processes; thus, their deregulation is usually apt to the occurrence of diverse diseases. Previous studies indicate that abnormally up-regulated miR-29a is associated with several diseases, such as human acute myeloid leukemia and diabetes; therefore, the proper level of miR-29a is critical for homeostasis. Herein, we observed that miR-29a was repressed by androgen/androgen receptor signaling in mouse epididymis by targeting a conserved androgen response element located 8 kb upstream of miR-29b1a loci. It is well known that multiple regulatory programs often form a complicated network. Here, we found that miR-29a reversibly suppressed androgen receptor and its target genes by targeting IGF1 and p53 pathways. miR-29b1a-overexpressing transgenic mice displayed epididymis hypoplasia partially similar to the phenotype of those mice with an impaired androgen-androgen receptor signal system. Taken together, the results demonstrated that there is a regulatory circuitry between the androgen signaling pathway and miR-29a in mouse epididymis that may be vital for epididymal development and functions.
MicroRNAs 参与了许多细胞过程；因此，它们的失调通常容易发生各种疾病。先前的研究表明，异常上调的 miR-29a 与多种疾病有关，如人类急性髓性白血病和糖尿病；因此，miR-29a 的适当水平对体内平衡至关重要。在这里，我们观察到 miR-29a 通过靶向位于 miR-29b1a 基因座上游 8kb 的保守雄激素反应元件，被雄激素/雄激素受体信号抑制在小鼠附睾中。众所周知，多种调控程序通常形成一个复杂的网络。在这里，我们发现 miR-29a 通过靶向 IGF1 和 p53 途径可逆性抑制雄激素受体及其靶基因。过表达 miR-29b1a 的转基因小鼠表现出附睾发育不良，部分类似于雄激素-雄激素受体信号系统受损的小鼠的表型。综上所述，研究结果表明，在小鼠附睾中，雄激素信号通路和 miR-29a 之间存在一个调节回路，这可能对附睾的发育和功能至关重要。
