LncRNA-412.25 activates the LIF/STAT3 signaling pathway in ovarian granulosa cells of Hu sheep by sponging miR-346
LncRNA-412.25 activates the LIF/STAT3 signaling pathway in ovarian granulosa cells of Hu sheep by sponging miR-346
复制标题
LncRNA-412.25通过海绵miR-346激活湖羊卵巢颗粒细胞中的LIF/STAT3信号通路
DOI：
10.1096/fj.202200632r
复制
发表时间：
2022
期刊：
影响因子：
--
通讯作者：
Feng Wang
中科院分区：
文献类型：
--
作者：
Xiaolei Yao;M A EI-Samahy;Xiaodan Li;Yongjin Bao;Jiahe Guo;Fan Yang;Zhibo Wang;Kang Li;Yanli Zhang;Feng Wang
尽管据报道长非编码RNA（lncRNA）可以调节卵泡发育和生殖疾病发病机制，但其潜在机制尚未阐明。在本研究中，对不同繁殖力的湖羊不同大小的健康卵泡的lncRNA表达谱进行了分析，发现了50 613个lncRNA。许多lncRNA在不同比较组之间存在差异表达。这项研究描述了一种新的转录本 lncRNA-412.25（来自直径 > 5 毫米的健康卵泡），它主要在高增殖组中表达，并定位于颗粒细胞 (GC) 的细胞质。 LncRNA-412.25敲低分别促进和抑制湖羊GC凋亡和增殖。有趣的是，lncRNA-412.25可以直接与miR-346结合，而miR-346可以靶向白血病抑制因子（LIF）基因。 lncRNA-412.25 的敲低通过下调 LIF 表达促进 GC 凋亡，而这种效应被 miR-346 减弱。此外，miR-346抑制剂减轻了lncRNA-412.25敲低引起的信号转导子和转录激活子3（STAT3）磷酸化蛋白的下调，这一点已通过免疫荧光分析得到验证。我们的结果表明，lncRNA-412.25 通过与 miR-346 结合，然后激活 LIF/STAT3 通路来调节湖羊的 GC 增殖和凋亡。这些发现为绵羊繁殖力的潜在机制提供了新的见解。
Although long non-coding RNAs (lncRNAs) are reported to regulate follicular development and reproductive disease pathogenesis, the underlying mechanisms have not been elucidated. In this study, lncRNA expression profiling of different-sized healthy follicles from Hu sheep with different prolificacy revealed 50 613 lncRNAs. Numerous lncRNAs were differentially expressed among different comparison groups. This study characterized one novel transcript, lncRNA-412.25 (from healthy follicles with a diameter of >5 mm), which was predominantly expressed in the high prolificacy group and localized to the cytoplasm of granulosa cells (GCs). LncRNA-412.25 knockdown promoted and inhibited Hu sheep GC apoptosis and proliferation, respectively. Interestingly, lncRNA-412.25 could directly bind to miR-346, which can target the gene of leukemia inhibitory factor (LIF). Knockdown of lncRNA-412.25 promoted GC apoptosis by downregulating LIF expression, where this effect was attenuated by miR-346. Moreover, the miR-346 inhibitor mitigated the lncRNA-412.25 knockdown-induced downregulation of phosphorylated protein of signal transducer and activator of transcription 3 (STAT3), which was validated using immunofluorescence analysis. Our results demonstrated that lncRNA-412.25 regulates GC proliferation and apoptosis in Hu sheep by binding to miR-346 and then activating the LIF/STAT3 pathway. These findings provide novel insights into the mechanisms underlying prolificacy in sheep.