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MiR-375 potentially enhances GnRH expression by targeting Sp1 in GT1-7 cells

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Abstract

Gonadotropin-releasing hormone (GnRH) is the initial central regulator of the animal reproduction system, which is crucial for puberty onset and fertility. However, the mechanisms regulating GnRH production and release remain unclear. In addition, few studies reported that miR-375 expressed in mouse hypothalamus, but up to now there are limited functional studies of miR-375 in regulating GnRH secretion. According to our recent findings that miR-375 was involved in regulating the synthesis and secretion of pituitary hormones, thus, we aimed to identify the role of miR-375 in regulating GnRH production in GT1-7 cells. Immunofluorescence results demonstrated that miR-375 was expressed in all of the GT1-7 cells. The functional studies showed that miR-375 overexpression enhanced GnRH mRNA expression level, but decreased the mRNA expressions of Sp1, Cebpb, Msx1, and Tle4. Transcriptomics analysis demonstrated Sp1 and Tle4 acted as the targeting genes of miR-375, and Sp1 negatively regulated Gnrh mRNA expression by binding to the Gnrh promoter. Thus, we conclude that miR-375 potentially enhances GnRH expression by targeting Sp1 and Tle4 in GT1-7 cells. Our results highlight a critical role of miR-375 in regulating GnRH production, which may provide a novel potential therapeutic approach to neuroendocrine-disorder-related dysfunctions.

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Funding

This work was supported by the National Key Research and Developmental Program of China (2018YFC1003504), the Natural Science Foundation of China (31430083, 31772692), and the Project of the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).

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Author notes

  1. Hongjiao Li and Xin Li contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Agrobiotechnology, College of Biological Sciences, China Agricultural University, Beijing, 10021, People’s Republic of China

    Hongjiao Li, Xin Li & Sheng Cui

  2. College of Veterinary Medicine, Yangzhou University, Yangzhou, 225009, Jiangsu, People’s Republic of China

    Hongjiao Li, Di Zhang & Sheng Cui

  3. Department of Biochemistry and Molecular Biology, Key Laboratory of Human Functional Genomics of Jiangsu Province, Nanjing Medical University, Nanjing, Jiangsu, People’s Republic of China

    Juxue Li

  4. Jiangsu Co-innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonoses, Yangzhou, 225009, Jiangsu, People’s Republic of China

    Sheng Cui

  5. Joint International Research Laboratory of Agriculture and Agri-Product Safety, the Ministry of Education of China, Yangzhou University, Yangzhou, 225009, Jiangsu, People’s Republic of China

    Sheng Cui

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  1. Hongjiao Li
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  2. Xin Li
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  3. Di Zhang
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Correspondence to Sheng Cui.

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Editor: Tetsuji Okamoto

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Li, H., Li, X., Zhang, D. et al. MiR-375 potentially enhances GnRH expression by targeting Sp1 in GT1-7 cells. In Vitro Cell.Dev.Biol.-Animal 57, 438–447 (2021). https://doi.org/10.1007/s11626-020-00447-4

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  • DOI: https://doi.org/10.1007/s11626-020-00447-4

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