| First Author | Liu T | Year | 2024 |
| Journal | Cell Prolif | Volume | 57 |
| Issue | 11 | Pages | e13686 |
| PubMed ID | 38831624 | Mgi Jnum | J:359284 |
| Mgi Id | MGI:7785623 | Doi | 10.1111/cpr.13686 |
| Citation | Liu T, et al. (2024) MicroRNA-3061 downregulates the expression of PAX7/Wnt/Ca(2+) signalling axis genes to induce premature ovarian failure in mice. Cell Prolif 57(11):e13686 |
| abstractText | 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/Ca(2+) 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/Ca(2+) 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/Ca(2+) signalling pathway genes. |
