文献类型： 外文期刊

作者： Liu, Shan-Shan ¹ ; Maguire, Eithne Margaret ³ ; Bai, Yin-Shan ⁴ ; Huang, Li ² ; Liu, Yurong ¹ ; Xu, Liping ² ; Fauzi, ¹ ;

作者机构： 1.Guangzhou Med Univ, Affiliated Canc Hosp & Inst, Guangzhou, Guangdong, Peoples R China

2.Guangzhou Med Univ, Lab Prot Modificat & Degradat, Sch Basic Med Sci, Guangzhou, Guangdong, Peoples R China

3.Queen Mary Univ London, Ctr Clin Pharmacol, William Harvey Res Inst, Barts & London Sch Med & Dent, London, England

4.South China Agr Univ, Natl Engn Res Ctr Breeding Swine Ind, Guangdong Prov Key Lab Agroanim Genom & Mol Breed, Coll Anim Sci, Guangzhou, Guangdong, Peoples R China

5.Guangzhou Med Univ, Key Lab Cardiovasc Dis, Affiliated Hosp 2, Sch Basic Med Sci, Guangzhou, Guangdong, Peoples R China

关键词： CHD1L; cell apoptosis; cell proliferation; cell cycle; MMP2; spermatogonial stem cell; stemness; miR-486; microRNAs

期刊名称：MOLECULAR AND CELLULAR BIOLOGY （ 影响因子：4.272； 五年影响因子：4.56 ）

ISSN： 0270-7306

年卷期： 2019 年 39 卷 4 期

页码：

收录情况： SCI

摘要： Spermatogonial stem cells (SSCs) are unipotent germ cells that are at the foundation of spermatogenesis and male fertility. However, the underlying molecular mechanisms governing SSC stemness and growth properties remain elusive. We have recently identified chromodomain helicase/ATPase DNA binding protein 1-like (Chd1l) as a novel regulator for SSC survival and self-renewal, but how these functions are controlled by Chd1l remains to be resolved. Here, we applied high-throughput small RNA sequencing to uncover the microRNA (miRNA) expression profiles controlled by Chd1l and showed that the expression levels of 124 miRNA transcripts were differentially regulated by Chd1l in SSCs. KEGG pathway analysis shows that the miRNAs that are differentially expressed upon Chd1l repression are significantly enriched in the pathways associated with stem cell pluripotency and proliferation. As a proof of concept, we demonstrate that one of the most highly upregulated miRNAs, miR-486, controls SSC stemness gene expression and growth properties. The matrix metalloproteinase 2 (MMP2) gene has been identified as a novel miR-486 target gene in the context of SSC stemness gene regulation and growth properties. Data from cotransfection experiments showed that Chd1l, miR486, and MMP2 work in concert in regulating SSC stemness gene expression and growth properties. Finally, our data also revealed that MMP2 regulates SSC stemness gene expression and growth properties through activating beta-catenin signaling by cleaving N-cadherin and increasing beta-catenin nuclear translocation. Our data demonstrate that Chd1l-miR-486-MMP2 is a novel regulatory axis governing SSC stemness gene expression and growth properties, offering a novel therapeutic opportunity for treating male infertility.