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MicroRNA-3061 downregulates the expression of PAX7/Wnt/Ca2+ signalling axis genes to induce premature ovarian failure in mice.
Liu, Te; Wen, Yichao; Cui, Zeyu; Chen, Haiyang; Lin, Jiajia; Xu, Jianghong; Chen, Danping; Zhu, Ying; Yu, Zhihua; Wang, Chunxia; Zhang, Bimeng.
Afiliación
  • Liu T; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Wen Y; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Cui Z; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Chen H; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Lin J; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Xu J; Department of Gynaecology, Jingan Hospital of Traditional Chinese Medicine, Shanghai, China.
  • Chen D; Department of Gynaecology, Jingan Hospital of Traditional Chinese Medicine, Shanghai, China.
  • Zhu Y; Department of Gynaecology, Jingan Hospital of Traditional Chinese Medicine, Shanghai, China.
  • Yu Z; Shanghai Geriatric Institute of Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, China.
  • Wang C; Department of Reproductive Medicine, Henan Province Hospital of Traditional Chinese Medicine, Henan, China.
  • Zhang B; Department of Acupuncture, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Cell Prolif ; : e13686, 2024 Jun 03.
Article en En | MEDLINE | ID: mdl-38831624
ABSTRACT
The in-depth mechanisms of microRNA regulation of premature ovarian failure (POF) remain unclear. Crispr-cas9 technology was used to construct transgenic mice. The qPCR and Western blot was used to detect the expression level of genes. H&E staining were used to detect ovarian pathological phenotypes. We found that the expression levels of microRNA-3061 were significantly higher in ovarian granulosa cells (OGCs) of POF mouse models than in controls. The miR-3061+/-/AMH-Cre+/- transgenic mice manifested symptoms of POF. RNA-Seq and luciferase reporter assay confirmed that the PAX7 was one of the target genes negatively regulated by microRNA-3061 (miR-3061-5p). Moreover, PAX7 mediated the expression of non-canonical Wnt/Ca2+ signalling pathway by binding to the motifs of promoters to stimulate the transcriptional activation of Wnt5a and CamK2a. In contrast, specific knock-in of microRNA-3061 in OGCs significantly downregulated the expression levels of PAX7 and inhibited the expression of downstream Wnt/Ca2+ signalling pathway. We also discerned a correlation between the expression levels of mRNAs of the Wnt/Ca2+ signalling pathway and the levels of E2 and FSH in POF patients by examining gene expression in the follicular fluid-derived exosomes of women. We confirmed that overexpression of microRNA-3061 induced proliferative inhibition of OGCs and ultimately induced POF in mice by suppressing the transcription factor PAX7 and downregulating expression levels of its downstream Wnt/Ca2+ signalling pathway genes.

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Prolif Año: 2024 Tipo del documento: Article País de afiliación: China

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: Cell Prolif Año: 2024 Tipo del documento: Article País de afiliación: China