MicroRNA-3061 downregulates the expression of PAX7/Wnt/Ca2+ signalling axis genes to induce premature ovarian failure in mice

Te Liu; Yichao Wen; Zeyu Cui; Haiyang Chen; Jiajia Lin; Jianghong Xu; Danping Chen; Ying Zhu; Zhihua Yu; Chunxia Wang; Bimeng Zhang

doi:10.1111/cpr.13686

Cell Proliferation ›› 2024, Vol. 57 ›› Issue (11) : e13686 DOI: 10.1111/cpr.13686

ORIGINAL ARTICLE

MicroRNA-3061 downregulates the expression of PAX7/Wnt/Ca²⁺ signalling axis genes to induce premature ovarian failure in mice

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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 noncanonical 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.

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Te Liu, Yichao Wen, Zeyu Cui, Haiyang Chen, Jiajia Lin, Jianghong Xu, Danping Chen, Ying Zhu, Zhihua Yu, Chunxia Wang, Bimeng Zhang. MicroRNA-3061 downregulates the expression of PAX7/Wnt/Ca²⁺ signalling axis genes to induce premature ovarian failure in mice. Cell Proliferation, 2024, 57(11): e13686 DOI:10.1111/cpr.13686

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