Li Duan, Wang Xiaoyan, Dang Yujie, Zhang Xinyue, Zhao Shidou, Lu Gang, Chan Wai-Yee, Leung Peter C K, Qin Yingying
Center for Reproductive Medicine, Cheeloo College of Medicine, Shandong University, Jinan, Shandong 250012, China.
Key Laboratory of Reproductive Endocrinology of Ministry of Education, Shandong University, Jinan, Shandong 250012, China.
Mol Ther Nucleic Acids. 2020 Nov 4;23:132-141. doi: 10.1016/j.omtn.2020.10.041. eCollection 2021 Mar 5.
Dysfunction of granulosa cells (GCs) leading to follicle atresia has been extensively studied as a major cause of premature ovarian insufficiency (POI), but the regulatory role of long non-coding RNAs (lncRNAs) in this process is still poorly understood. Here, we show that the lncRNA or (granulosa cell-associated transcript 1) is downregulated in GCs from patients with biochemical POI (bPOI), and we show a significant correlation between downregulated and serum levels of follicle-stimulating hormone and anti-Müllerian hormone. Downregulation of inhibited G1/S cell cycle progression and thus inhibited the proliferation of GCs. Mechanistically, we show that competes with cyclin-dependent kinase inhibitor 1B () mRNA for polypyrimidine tract-binding protein 1 (PTBP1) binding, and thus decreased might promote PTBP1 binding to mRNA and thereby initiate CDKN1B protein (p27) translation. Together, our results suggest that downregulation of under conditions of bPOI inhibits the proliferation of GCs through PTBP1-dependent p27 regulation, thus suggesting a novel form of lncRNA-mediated epigenetic regulation of GC function that contributes to the pathogenesis of POI.
颗粒细胞（GCs）功能障碍导致卵泡闭锁已被广泛研究，这是卵巢早衰（POI）的主要原因，但长链非编码RNA（lncRNAs）在此过程中的调控作用仍知之甚少。在这里，我们发现lncRNA 或（颗粒细胞相关转录本1）在生化性POI（bPOI）患者的GCs中表达下调，并且我们发现下调的 与卵泡刺激素和抗苗勒管激素的血清水平之间存在显著相关性。 的下调抑制了G1/S细胞周期进程，从而抑制了GCs的增殖。从机制上讲，我们发现 与细胞周期蛋白依赖性激酶抑制剂1B（ ）mRNA竞争多嘧啶序列结合蛋白1（PTBP1）的结合，因此 的减少可能促进PTBP1与 mRNA的结合，从而启动CDKN1B蛋白（p27）的翻译。总之，我们的结果表明，在bPOI条件下 的下调通过PTBP1依赖的p27调节抑制了GCs的增殖，从而提示了一种新的lncRNA介导的GC功能表观遗传调控形式，这有助于POI的发病机制。
