miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling

Chao Yang; Chencheng Yao; Ruhui Tian; Zijue Zhu; Liangyu Zhao; Peng Li; Huixing Chen; Yuhua Huang; Erlei Zhi; Yuehua Gong; Yunjing Xue; Hong Wang; Qingqing Yuan; Zuping He; Zheng Li

Molecular Therapy: Nucleic Acids (Mar 2019)

miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling

Chao Yang,
Chencheng Yao,
Ruhui Tian,
Zijue Zhu,
Liangyu Zhao,
Peng Li,
Huixing Chen,
Yuhua Huang,
Erlei Zhi,
Yuehua Gong,
Yunjing Xue,
Hong Wang,
Qingqing Yuan,
Zuping He,
Zheng Li

Affiliations

Chao Yang: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; Nanjing Medical University, 101 Longmian Dadao, Jiangning District, Nanjing 210029, China
Chencheng Yao: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China
Ruhui Tian: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Zijue Zhu: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Liangyu Zhao: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Peng Li: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Huixing Chen: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Yuhua Huang: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Erlei Zhi: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Yuehua Gong: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Yunjing Xue: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Hong Wang: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China
Qingqing Yuan: Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Renji Hospital, School of Medicine, Shanghai Jiao Tong University, 845 Lingshan Road, Shanghai 200135, China
Zuping He: Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; School of Medicine, Hunan Normal University, 371 Tongzipo Road, Changsha, Hunan 410013, China; Corresponding author: Zuping He, School of Medicine, Hunan Normal University, 371 Tongzipo Road, Changsha, Hunan 410013, China.
Zheng Li: Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China; Shanghai Key Laboratory of Reproductive Medicine, Shanghai 200025, China; Corresponding author: Zheng Li, Department of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, China.

Journal volume & issue: Vol. 14
pp. 1 – 19

Abstract

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MicroRNAs (miRNAs) play important roles in mammalian spermatogenesis, which is highly dependent on Sertoli cells. However, the functions and mechanisms of miRNAs in regulating human Sertoli cells remain largely unknown. Here, we report that hsa-miR-202-3p mediates the proliferation, apoptosis, and synthesis function of human Sertoli cells. miR-202-3p was upregulated in Sertoli cells of Sertoli cell-only syndrome (SCOS) patients compared with obstructive azoospermia (OA) patients with normal spermatogenesis. Overexpression of miR-202-3p induced Sertoli cell apoptosis and inhibited cell proliferation and synthesis, and the effects were opposite when miR-202-3p was knocked down. Lipoprotein receptor-related protein 6 (LRP6) and Cyclin D1 of the Wnt/β-catenin signaling pathway were identified as direct targets of miR-202-3p in Sertoli cells, which were validated by bioinformatics tools and dual-luciferase reporter assay. Differentially expressed LRP6 and Cyclin D1 between OA and SCOS Sertoli cells were also verified. LRP6 small interfering RNA (siRNA) interference not only mimicked the effects of miR-202-3p overexpression, but also antagonized the effects of miR-202-3p inhibition on Sertoli cells. Collectively, miR-202-3p controls the proliferation, apoptosis, and synthesis function of human Sertoli cells via targeting LRP6 and Cyclin D1 of the Wnt/β-catenin signaling pathway. This study thus provides a novel insight into fate determinations of human Sertoli cells and niche of human testis. Keywords: human Sertoli cells, miR-202-3p, proliferation and apoptosis, synthesis, LRP6, Cyclin D1, Wnt/β-catenin

Published in Molecular Therapy: Nucleic Acids

ISSN: 2162-2531 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: https://www.cell.com/molecular-therapy-family/nucleic-acids/latest-content

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