miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling
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 s...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-03-01
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| Series: | Molecular Therapy: Nucleic Acids |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S216225311830283X |
| _version_ | 1819295247637676032 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Chao Yang |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-24T04:39:11Z |
| format | Article |
| id | doaj.art-58a58259ce774e6f9682a059ea95f89f |
| institution | Directory Open Access Journal |
| issn | 2162-2531 |
| language | English |
| last_indexed | 2024-12-24T04:39:11Z |
| publishDate | 2019-03-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Molecular Therapy: Nucleic Acids |
| spelling | doaj.art-58a58259ce774e6f9682a059ea95f89f2022-12-21T17:14:55ZengElsevierMolecular Therapy: Nucleic Acids2162-25312019-03-0114119miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin SignalingChao Yang0Chencheng Yao1Ruhui Tian2Zijue Zhu3Liangyu Zhao4Peng Li5Huixing Chen6Yuhua Huang7Erlei Zhi8Yuehua Gong9Yunjing Xue10Hong Wang11Qingqing Yuan12Zuping He13Zheng Li14Department 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, ChinaDepartment 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, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaDepartment of Andrology, Urologic Medical Center, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, 100 Haining Road, Shanghai 200080, ChinaShanghai 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, ChinaShanghai 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.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.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-cateninhttp://www.sciencedirect.com/science/article/pii/S216225311830283X |
| spellingShingle | 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 miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling Molecular Therapy: Nucleic Acids |
| title | miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling |
| title_full | miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling |
| title_fullStr | miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling |
| title_full_unstemmed | miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling |
| title_short | miR-202-3p Regulates Sertoli Cell Proliferation, Synthesis Function, and Apoptosis by Targeting LRP6 and Cyclin D1 of Wnt/β-Catenin Signaling |
| title_sort | mir 202 3p regulates sertoli cell proliferation synthesis function and apoptosis by targeting lrp6 and cyclin d1 of wnt β catenin signaling |
| url | http://www.sciencedirect.com/science/article/pii/S216225311830283X |
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