Abstract
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.
Highlights
Up-regulated miR-29a is associated with several diseases, so miR-29a repression is important for homeostasis
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
Our results showed that miR-29a was repressed by androgen/AR in mouse epididymis
Summary
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/p85␣p53 pathways in mouse epididymis. 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. MiR-29a expression is greatly enhanced in patients with invasive breast carcinomas compared with non-invasive hyperplasias [14] All these data indicate that abnormal up-regulation of miR-29a is harmful; miR-29a expression should be properly suppressed. In the male reproductive system, especially in epididymis, the androgen pathway plays very important regulatory roles in development, function, gene expression, and even miRNA expression. Our results demonstrated a regulatory circuitry between androgen/AR signaling pathway and miR-29a that may be important for epididymal development and functions
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