<i>Lin28b-let-7</i> Modulates mRNA Expression of <i>GnRH1</i> Through Multiple Signaling Pathways Related to Glycolysis in GT1-7 Cells
<i>Lin28b</i> and <i>let-7</i> miRNA regulate mammalian pubertal initiation and Gonadotropin-releasing hormone (GnRH) production. However, it remains unclear which signaling pathways <i>Lin28b</i> regulates to modulate GnRH production. In this study, the mRNA expr...
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| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2025-01-01
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| Series: | Animals |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2076-2615/15/2/120 |
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| Summary: | <i>Lin28b</i> and <i>let-7</i> miRNA regulate mammalian pubertal initiation and Gonadotropin-releasing hormone (GnRH) production. However, it remains unclear which signaling pathways <i>Lin28b</i> regulates to modulate GnRH production. In this study, the mRNA expression levels of <i>Lin28b</i> and <i>let-7</i> in the pubertal and juvenile goat hypothalamus and pituitary gland were detected, and <i>Lin28b</i> expression in the pubertal hypothalamus decreased significantly compared with that in juvenile tissues. It was predicted that <i>Lin28b</i> might inhibit <i>GnRH1</i> expression, which was verified in the GnRH-producing cell model GT1-7 cells. <i>Lin28b</i> inhibited <i>GnRH1</i> expression and promoted Kiss1/Gpr54 signaling. The pyruvate content and the expression of <i>Hif1a</i> and <i>Hk2</i>, which were related to glycolysis, were also promoted by <i>Lin28b</i> overexpression. Additionally, 77 differentially expressed miRNAs (DEMIs) in <i>Lin28b</i>-overexpressed GT1-7 cells were identified. Bioinformatics analysis and mRNA expression of the target genes of DEMIs revealed that the MAPK and PI3K-AKT-mTOR signaling pathways were key pathways that involved the regulatory effect of <i>Lin28b</i> on GnRH. In GT1-7 cells, <i>GnRH1</i> expression was suppressed by blocking mTOR signaling with rapamycin, which was rescued by <i>Lin28b</i> overexpression. These results indicate that <i>Lin28b-let-7</i> regulates <i>GnRH1</i> expression through several pathways, including the Kiss1/Gpr54, MAPK, and mTOR signaling pathways, which are all related to glucose metabolism and provide new insights into the molecular mechanism of the regulatory role of <i>Lin28b</i> on GnRH production. |
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| ISSN: | 2076-2615 |