LncRNA MEG3 regulates ASK1/JNK axis-mediated apoptosis and autophagy via sponging miR-23a in granulosa cells of yak tertiary follicles.
LncRNA MEG3 regulates ASK1/JNK axis-mediated apoptosis and autophagy via sponging miR-23a in granulosa cells of yak tertiary follicles.
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DOI：
10.1016/j.cellsig.2023.110680
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发表时间：
2023-04
影响因子：
4.8
通讯作者：
Xiaohong Han;Yangyang Pan;Jiangfeng Fan;Meng Wang;Libin Wang;Jinglei Wang;S. Y. Afedo;Ling Zhao-L
中科院分区：
文献类型：
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作者：
Xiaohong Han;Yangyang Pan;Jiangfeng Fan;Meng Wang;Libin Wang;Jinglei Wang;S. Y. Afedo;Ling Zhao-L
颗粒细胞（GC）的凋亡和自噬与卵泡发育和闭锁高度相关。也有报道称它们与 LncRNA MEG3、miR-23a 和凋亡信号调节激酶 1 (ASK-1) 有关。然而，它们与卵泡发育的关系以及卵泡刺激素 (FSH) 或黄体生成素 (LH) 调节这一过程的程度仍然未知。在这里，我们发现 ASK1 和 JNK 在促性腺激素依赖性卵泡的 GC 中表达，并且与二级卵泡和格拉夫卵泡相比，牦牛第三卵泡中的这些水平显着较高 (p < 0.05)。然后，研究了LncRNA MEG3 / miR-23a通过ASK1/JNK（c-Jun N端激酶）对牦牛GC细胞凋亡和自噬的影响。过表达LncRNA MEG3降低了miR-23a水平和p-967蛋白表达，但增强了ASK1和JNKmRNA水平以及t-ASK1、p-845、t-JNK和p-JNK蛋白水平。 LncRNA MEG3 的上调促进细胞凋亡，同时减弱自噬。双荧光素酶报告基因检测也证实了miR-23a与LncRNA MEG3和ASK1结合位点之间的靶向关系。并且，LncRNA MEG3和miR-23a之间的关系被观察为负反馈调节，LncRNA MEG3和miR-23a水平的变化可以改变牦牛GC中ASK1/JNK轴的表达。此外，在牦牛 GC 中验证了 FSH (10 μg/mL) 或 LH (100 μg/mL) 逆转 LncRNA MEG3 对 miR-23a 水平和 ASK1/JNK 轴介导的细胞凋亡和自噬影响的能力。这对于减少牦牛第三卵泡的异常卵泡闭锁具有显着的益处。
Apoptosis and autophagy in granulosa cells (GCs) are highly related to follicular development and atresia. It has also been reported that they are related to LncRNA MEG3, miR-23a and apoptosis signal-regulating kinase 1 (ASK-1). However, their relationship to follicular development and the extent to which follicle stimulating hormone (FSH) or luteinizing hormone (LH) can regulate this process remain unknown. Here, we found that ASK1 and JNK were expressed in the GCs of gonadotropin-dependent follicles, and those levels were significantly higher (p< 0.05) in yak Tertiary follicles compared to that of Secondary follicles and Graafian follicles. Then, the effect ofLncRNA MEG3 / miR-23aon apoptosis and autophagy viaASK1/JNK(c-Jun N-terminal kinase) in yak GCs was studied. OverexpressingLncRNA MEG3reducedmiR-23alevels and p-967 protein expression, but enhancedASK1andJNKmRNA levels as well as t-ASK1, p-845, t-JNK, and p-JNK proteins levels. And Up-regulation ofLncRNA MEG3promoted apoptosis while attenuating autophagy. The targeting relationship betweenmiR-23aand the binding sites ofLncRNA MEG3andASK1was also confirmed with the dual luciferase reporter assay. And, the relationship betweenLncRNA MEG3andmiR-23a was observed as a negative feedback regulation, and changes inLncRNA MEG3andmiR-23alevels can alter the expression ofASK1/JNKaxis in yaks GCs. In addition, FSH (10 μg/mL) or LH (100 μg/mL) ability to reverse the effects ofLncRNA MEG3onmiR-23alevels andASK1/JNKaxis-mediated apoptosis and autophagy was verified in yak GCs. This is significantly beneficial for decreasing abnormal follicular atresia for yaks tertiary follicles.