Oncotarget

Research Papers: Pathology:

MiRNA-133b promotes the proliferation of human Sertoli cells through targeting GLI3

Chencheng Yao, Min Sun, Qingqing Yuan, Minghui Niu, Zheng Chen, Jingmei Hou, Hong Wang, Liping Wen, Yun Liu, Zheng Li and Zuping He _

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Oncotarget. 2016; 7:2201-2219. https://doi.org/10.18632/oncotarget.6876

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Abstract

Chencheng Yao1, Min Sun1, Qingqing Yuan1, Minghui Niu1, Zheng Chen1, Jingmei Hou1, Hong Wang1, Liping Wen1, Yun Liu1, Zheng Li2 and Zuping He1,2,3,4

1 State Key Laboratory of Oncogenes and Related Genes, Renji-Med X Clinical Stem Cell Research Center, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China

2 Department of Urology, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai Institute of Andrology, Shanghai, China

3 Shanghai Key Laboratory of Assisted Reproduction and Reproductive Genetics, Shanghai, China

4 Shanghai Key Laboratory of Reproductive Medicine, Shanghai, China

Correspondence to:

Zuping He, email:

Keywords: human Sertoli cells, global miRNA profile, Sertoli-cell-only syndrome, miRNA-133b, cell proliferation, Pathology Section

Received: September 01, 2015 Accepted: January 03, 2016 Published: January 10, 2016

Abstract

Sertoli cells play critical roles in regulating spermatogenesis and they can be reprogrammed to the cells of other lineages, highlighting that they have significant applications in reproductive and regenerative medicine. The fate determinations of Sertoli cells are regulated precisely by epigenetic factors. However, the expression, roles, and targets of microRNA (miRNA) in human Sertoli cells remain unknown. Here we have for the first time revealed that 174 miRNAs were distinctly expressed in human Sertoli cells between Sertoli-cell-only syndrome (SCOS) patients and obstructive azoospermia (OA) patients with normal spermatogenesis using miRNA microarrays and real time PCR, suggesting that these miRNAs may be associated with the pathogenesis of SCOS. MiR-133b is upregulated in Sertoli cells of SCOS patients compared to OA patients. Proliferation assays with miRNA mimics and inhibitors showed that miR-133b enhanced the proliferation of human Sertoli cells. Moreover, we demonstrated that GLI3 was a direct target of miR-133b and the expression of Cyclin B1 and Cyclin D1 was enhanced by miR-133b mimics but decreased by its inhibitors. Gene silencing of GLI3 using RNA inference stimulated the growth of human Sertoli cells. Collectively, miR-133b promoted the proliferation of human Sertoli cells by targeting GLI3. This study thus sheds novel insights into epigenetic regulation of human Sertoli cells and the etiology of azoospermia and offers new targets for treating male infertility


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