An androgen receptor-microrna-29a regulatory circuitry in mouse epididymis

J Biol Chem. 2013 Oct 11;288(41):29369-81. doi: 10.1074/jbc.M113.454066. Epub 2013 Aug 19.

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.

Keywords: Androgen; Androgen Receptor; Epididymis; Gene Regulation; MicroRNA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Androgens / pharmacology
  • Animals
  • Blotting, Western
  • Cell Line
  • Cell Line, Tumor
  • Epididymis / metabolism*
  • Gene Expression Regulation / drug effects
  • HEK293 Cells
  • Humans
  • Insulin-Like Growth Factor I / genetics
  • Insulin-Like Growth Factor I / metabolism
  • MCF-7 Cells
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • MicroRNAs / genetics*
  • Models, Genetic
  • Orchiectomy
  • RNA Interference
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Androgen / genetics*
  • Receptors, Androgen / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / genetics*
  • Tumor Suppressor Protein p53 / genetics
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • Androgens
  • MIRN29 microRNA, mouse
  • MicroRNAs
  • Receptors, Androgen
  • Tumor Suppressor Protein p53
  • insulin-like growth factor-1, mouse
  • Insulin-Like Growth Factor I