Circ_0008219 regulates proliferation and apoptosis in goat granulosa cells via a feedback loop with the transcription factor YY1

Circ_0008219 通过与转录因子 YY1 的反馈回路调控山羊颗粒细胞的增殖和凋亡。

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作者:Hu Tao,Fan Jiang,Nian Zhang,Yi Shuai,Hua Zhao,Juan Yang,Feng Zhang,Aishao Shangguan,Qi Xiong

Abstract

Background: Circular RNAs (circRNAs) are a class of competitive endogenous RNAs (ceRNAs) widely found in animals, they can directly or indirectly affect the proliferation and apoptosis of granulosa cells (GCs) by regulating microRNA (miRNA) pathways. Preliminary research findings indicate that circ_0008219 is differentially expressed in pre-ovulatory follicles between Boer goats and Macheng black goats, suggesting its potential critical role in goat ovulation. As a potential target, its specific functions and regulatory mechanisms warrant further investigation. Results: A feedback loop of the YY1/circ_0008219/miR-130b-5p/FZD7 axis was constructed to elucidate the function and regulatory mechanism of circ_0008219 promoting GCs proliferation and suppressing apoptosis. Subsequent validation experiments were conducted in vitro using GCs. In our experiments, we identified circ_0008219 as a ceRNA in goat GCs that promoted proliferation. Through bioinformatics prediction and dual-luciferase reporter assays, we confirmed that circ_0008219 acts as a sponge for miR-130b-5p, preventing its binding to FZD7 mRNA and thereby increasing the expression of FZD7. This interaction also influenced the proliferation and apoptosis of goat GCs. Moreover, the transcription factor YY1 was found to form a feedback loop with circ_0008219 via the linkage of miR-130b-5p. Conclusions: Our study validated the biological function of the TF-circRNA-miRNA-mRNA feedback loop in goat GCs and revealed the potential regulatory mechanism by which circ_0008219 functions as a ceRNA in goat GCs, thus provide new insights into the mechanisms of regulated ovarian follicles development in female goats. Supplementary Information: The online version contains supplementary material available at 10.1186/s12864-026-12552-x.

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