MicroRNAs (miRs) play a key role in the control of gene expression in a wide array of tissue systems, where their functions include the regulation of self-renewal, cellular differentiation, proliferation and apoptosis. However, the function and mechanisms of individual miRs in regulating spermatogonial stem cell (SSC) homeostasis remain unclear. In the present study, we report for the first time that miR-224 is highly expressed in mouse SSCs. Functional assays using miRNA mimics and inhibitors reveal that miR-224 is essential for differentiation of SSCs. Mechanistically, miR-224 promotes differentiation of SSCs via targeting doublesex and Mab-3-related transcription factor 1 (DMRT1). Moreover, WNT/β-catenin signalling pathway is involved in miR-224-mediated regulation of SSCs self-renewal. We further demonstrate that miR-224 overexpression increases the expression of GFRα1 and PLZF, accompanied by the down-regulation of DMRT1 in mouse testes. Our findings provide novel insights into molecular mechanisms regulating differentiation of SSCs and may have important implications for regulating male reproduction.
Keywords: DMRT1; differentiation; miR-224; reproduction; spermatogonial stem cells.
© 2016 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.