FTO demethylates regulates cell-cycle progression by controlling CCND1 expression in luteinizing goat granulosa cells

Dongxu Li,Lei Zhou,Zifei Liu,Zhen Zhang, Weijia Mao, Wangwang Shi, Minghui Zhu,Feng Wang,Yongjie Wan

THERIOGENOLOGY(2024)

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摘要
In mammals, N6-methyladenosine (m6A) stands out as one of the most abundant internal mRNA modifications and plays a crucial role in follicular development. Nonetheless, the precise mechanism by which the demethylase FTO regulates the progression of the goat luteinizing granulosa cells (LGCs) cycle remains to be elucidated. In our study, we primarily assessed the protein and mRNA expression levels of genes using Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR), cell proliferation via EdU, cell viability with CCK-8, and apoptosis and cell cycle progression through flow cytometry. Here, the results demonstrated that knockdown of FTO significantly enhanced apoptosis, impeded cell proliferation, and increased autophagy levels in goat LGCs. Furthermore, the silencing of FTO substantially reduced cyclin D1 (CCND1) expression through the recognition and degradation of YTHDF2, consequently prolonging the cell cycle progression. This study sheds light on the mechanism by which FTO demethylation governs cell cycle progression by controlling the expression of CCND1 in goat LGCs, underscoring the dynamic role of m6A modification in the regulation of cell cycle progression.
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关键词
Luteinizing granulosa cells,FTO,YTHDF2,CCND1,Cell cycle
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