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Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs

OBJECTIVE: Thymopentin (5TP) significantly improved typical murine premature ovarian failure (POF) symptoms induced by a high‐fat and high‐sugar (HFHS) diet. However, its effect and mechanism remain unclear. MATERIALS AND METHODS: RNA‐Seq was used to detect the differentially expressed genes among e...

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Autores principales: Liu, Te, Jing, Fangyuan, Huang, Peirong, Geng, Zixiang, Xu, Jianghong, Li, Jiahui, Chen, Danping, Zhu, Ying, Wang, Zhenxin, Huang, Willian, Chen, Chuan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349654/
https://www.ncbi.nlm.nih.gov/pubmed/34180104
http://dx.doi.org/10.1111/cpr.13089
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author Liu, Te
Jing, Fangyuan
Huang, Peirong
Geng, Zixiang
Xu, Jianghong
Li, Jiahui
Chen, Danping
Zhu, Ying
Wang, Zhenxin
Huang, Willian
Chen, Chuan
author_facet Liu, Te
Jing, Fangyuan
Huang, Peirong
Geng, Zixiang
Xu, Jianghong
Li, Jiahui
Chen, Danping
Zhu, Ying
Wang, Zhenxin
Huang, Willian
Chen, Chuan
author_sort Liu, Te
collection PubMed
description OBJECTIVE: Thymopentin (5TP) significantly improved typical murine premature ovarian failure (POF) symptoms induced by a high‐fat and high‐sugar (HFHS) diet. However, its effect and mechanism remain unclear. MATERIALS AND METHODS: RNA‐Seq was used to detect the differentially expressed genes among each group. HFHS‐induced POF mouse model was generated and injected with siRNA using Poly (lactic‐co‐glycolic acid) (PLGA) as a carrier. RESULTS: RNA‐Seq suggested that 5TP promoted the expression of Yin Yang 2 (YY2) in mouse ovarian granulosa cell (mOGC) of HFHS‐POF mice. Luciferase reporter assay indicated that 5TP promoted the binding of YY2 to the specific sequence C(C/T)AT(G/C)(G/T) on the Lin28A promoter and promoted Lin28A transcription and expression. We continuously injected PLGA‐cross‐linked siRNA nanoparticles targeting YY2 into HFHS‐POF mice (siYY2@PLGA), which significantly reduced the therapeutic effect of 5TP. siYY2@PLGA injection also significantly attenuated the upregulation of Lin28a expression in mOGCs induced by 5TP and enhanced the expression of let‐7 family microRNAs, thereby inhibiting the proliferation and division of mOGCs. qPCR results showed that there was a significant difference in the expression levels of exosome‐derived Yy2 mRNAs between POF patients and normal women, and that there was a specific correlation between the expression level of exosome‐derived Yy2 and the peripheral concentrations of the blood hormones pregnenolone, progesterone and oestradiol. CONCLUSIONS: Thymopentin promotes the transcriptional activation of Lin28A via stimulating transcription factor YY2 expression, inhibits the activity of let‐7 family microRNAs and alleviates the ageing of ovarian granulosa cells, ultimately achieving a therapeutic effect on POF in mice.
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spelling pubmed-83496542021-08-15 Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs Liu, Te Jing, Fangyuan Huang, Peirong Geng, Zixiang Xu, Jianghong Li, Jiahui Chen, Danping Zhu, Ying Wang, Zhenxin Huang, Willian Chen, Chuan Cell Prolif Original Articles OBJECTIVE: Thymopentin (5TP) significantly improved typical murine premature ovarian failure (POF) symptoms induced by a high‐fat and high‐sugar (HFHS) diet. However, its effect and mechanism remain unclear. MATERIALS AND METHODS: RNA‐Seq was used to detect the differentially expressed genes among each group. HFHS‐induced POF mouse model was generated and injected with siRNA using Poly (lactic‐co‐glycolic acid) (PLGA) as a carrier. RESULTS: RNA‐Seq suggested that 5TP promoted the expression of Yin Yang 2 (YY2) in mouse ovarian granulosa cell (mOGC) of HFHS‐POF mice. Luciferase reporter assay indicated that 5TP promoted the binding of YY2 to the specific sequence C(C/T)AT(G/C)(G/T) on the Lin28A promoter and promoted Lin28A transcription and expression. We continuously injected PLGA‐cross‐linked siRNA nanoparticles targeting YY2 into HFHS‐POF mice (siYY2@PLGA), which significantly reduced the therapeutic effect of 5TP. siYY2@PLGA injection also significantly attenuated the upregulation of Lin28a expression in mOGCs induced by 5TP and enhanced the expression of let‐7 family microRNAs, thereby inhibiting the proliferation and division of mOGCs. qPCR results showed that there was a significant difference in the expression levels of exosome‐derived Yy2 mRNAs between POF patients and normal women, and that there was a specific correlation between the expression level of exosome‐derived Yy2 and the peripheral concentrations of the blood hormones pregnenolone, progesterone and oestradiol. CONCLUSIONS: Thymopentin promotes the transcriptional activation of Lin28A via stimulating transcription factor YY2 expression, inhibits the activity of let‐7 family microRNAs and alleviates the ageing of ovarian granulosa cells, ultimately achieving a therapeutic effect on POF in mice. John Wiley and Sons Inc. 2021-06-28 /pmc/articles/PMC8349654/ /pubmed/34180104 http://dx.doi.org/10.1111/cpr.13089 Text en © 2021 The Authors. Cell Proliferation published by John Wiley & Sons Ltd. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Te
Jing, Fangyuan
Huang, Peirong
Geng, Zixiang
Xu, Jianghong
Li, Jiahui
Chen, Danping
Zhu, Ying
Wang, Zhenxin
Huang, Willian
Chen, Chuan
Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs
title Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs
title_full Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs
title_fullStr Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs
title_full_unstemmed Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs
title_short Thymopentin alleviates premature ovarian failure in mice by activating YY2/Lin28A and inhibiting the expression of let‐7 family microRNAs
title_sort thymopentin alleviates premature ovarian failure in mice by activating yy2/lin28a and inhibiting the expression of let‐7 family micrornas
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8349654/
https://www.ncbi.nlm.nih.gov/pubmed/34180104
http://dx.doi.org/10.1111/cpr.13089
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