Int J Biol Sci 2019; 15(4):857-869. doi:10.7150/ijbs.30611

Research Paper

MicroRNA-322 Regulates Self-renewal of Mouse Spermatogonial Stem Cells through Rassf8

Yinjuan Wang1*, Xiaoyong Li1*, Xiaowen Gong1, Yongqiang Zhao1, Ji Wu1,2,3,4✉

1. Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Bio-X Institutes, Shanghai Jiao Tong University, Shanghai 200240, China
2. Key Laboratory of Fertility Preservation and Maintenance of Ministry of Education, Ningxia Medical University, Yinchuan 750004, China
3. Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China
4. State Key laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200032, China
* These authors contribute equally to this work

Abstract

Spermatogonial stem cells (SSCs) are essential for spermatogenesis and male fertility. MicroRNAs (miRs) are key regulators of gene expression involved in self-renewal, differentiation, and apoptosis. However, the function and mechanisms of individual miR in regulating self-renewal and differentiation of SSCs remain unclear. Here, we report for the first time that miR-322 regulates self-renewal of SSCs. Functional assays revealed that miR-322 was essential for SSC self-renewal. Mechanistically, miR-322 promoted SSC self-renewal by targeting RASSF8 (ras association domain family 8). Moreover, the WNT/β-catenin signaling pathway was involved in the miR-322-mediated regulation. Furthermore, miR-322 overexpression increased GFRα1, ETV5 and PLZF expression but decreased STRA8, C-KIT and BCL6 expression. Our study provides not only a novel insight into molecular mechanisms regulating SSC self-renewal but also a basis for the diagnosis, treatment, and prevention of male infertility.

Keywords: miRNA-322, Rassf8, SSCs, slef-renewal, WNT/β-catenin signaling pathway

This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY-NC) license (https://creativecommons.org/licenses/by-nc/4.0/). See http://ivyspring.com/terms for full terms and conditions.
How to cite this article:
Wang Y, Li X, Gong X, Zhao Y, Wu J. MicroRNA-322 Regulates Self-renewal of Mouse Spermatogonial Stem Cells through Rassf8. Int J Biol Sci 2019; 15(4):857-869. doi:10.7150/ijbs.30611. Available from http://www.ijbs.com/v15p0857.htm