An Androgen Receptor-MicroRNA-29a Regulatory Circuitry in Mouse Epididymis*

Background: Abnormally up-regulated miR-29a is associated with several diseases, so miR-29a repression is important for homeostasis. Results: miR-29a was repressed by androgen system and inversely inhibited AR expression by targeting IGF1 and CDC42/p85α-p53 pathways in mouse epididymis. Conclusion: There is an androgen receptor-miR-29a regulatory circuitry in mouse epididymis. Significance: The mutual repression between miR-29a and AR may be important for epididymal development and functions. 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.