<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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2025-01-01
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| author | Yujing Xie Xin Li Meng Wang Mingxing Chu Guiling Cao |
| author_facet | Yujing Xie Xin Li Meng Wang Mingxing Chu Guiling Cao |
| author_sort | Yujing Xie |
| collection | DOAJ |
| description | <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. |
| format | Article |
| id | doaj-art-6d3d9322cabb4d799fa00ce155052d2b |
| institution | Kabale University |
| issn | 2076-2615 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Animals |
| spelling | doaj-art-6d3d9322cabb4d799fa00ce155052d2b2025-01-24T13:17:39ZengMDPI AGAnimals2076-26152025-01-0115212010.3390/ani15020120<i>Lin28b-let-7</i> Modulates mRNA Expression of <i>GnRH1</i> Through Multiple Signaling Pathways Related to Glycolysis in GT1-7 CellsYujing Xie0Xin Li1Meng Wang2Mingxing Chu3Guiling Cao4School of Agriculture and Biology, Liaocheng University, Liaocheng 252059, ChinaSchool of Agriculture and Biology, Liaocheng University, Liaocheng 252059, ChinaSchool of Agriculture and Biology, Liaocheng University, Liaocheng 252059, ChinaState Key Laboratory of Animal Biotech Breeding, Institute of Animal Science, Chinese Academy of Agricultural Sciences, Beijing 100193, ChinaSchool of Agriculture and Biology, Liaocheng University, Liaocheng 252059, China<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.https://www.mdpi.com/2076-2615/15/2/120<i>Lin28b-let-7</i>GnRHglycolysisMAPKmTOR |
| spellingShingle | Yujing Xie Xin Li Meng Wang Mingxing Chu Guiling Cao <i>Lin28b-let-7</i> Modulates mRNA Expression of <i>GnRH1</i> Through Multiple Signaling Pathways Related to Glycolysis in GT1-7 Cells Animals <i>Lin28b-let-7</i> GnRH glycolysis MAPK mTOR |
| title | <i>Lin28b-let-7</i> Modulates mRNA Expression of <i>GnRH1</i> Through Multiple Signaling Pathways Related to Glycolysis in GT1-7 Cells |
| title_full | <i>Lin28b-let-7</i> Modulates mRNA Expression of <i>GnRH1</i> Through Multiple Signaling Pathways Related to Glycolysis in GT1-7 Cells |
| title_fullStr | <i>Lin28b-let-7</i> Modulates mRNA Expression of <i>GnRH1</i> Through Multiple Signaling Pathways Related to Glycolysis in GT1-7 Cells |
| title_full_unstemmed | <i>Lin28b-let-7</i> Modulates mRNA Expression of <i>GnRH1</i> Through Multiple Signaling Pathways Related to Glycolysis in GT1-7 Cells |
| title_short | <i>Lin28b-let-7</i> Modulates mRNA Expression of <i>GnRH1</i> Through Multiple Signaling Pathways Related to Glycolysis in GT1-7 Cells |
| title_sort | i lin28b let 7 i modulates mrna expression of i gnrh1 i through multiple signaling pathways related to glycolysis in gt1 7 cells |
| topic | <i>Lin28b-let-7</i> GnRH glycolysis MAPK mTOR |
| url | https://www.mdpi.com/2076-2615/15/2/120 |
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