ABSTRACT

Polycystic ovary syndrome (PCOS) causes anovulatory infertility in women of reproductive age, but etiopathogenesis of PCOS remains undetermined. Taurine up-regulated 1 (TUG1), an evolutionarily conserved long non-coding RNA, performs various biological functions; however, the role of TUG1 in PCOS remains unclear. Herein, TUG1 expression was assayed in granulosa cells (GCs) of 100 patients with PCOS and 100 control participants. Receiver operating characteristic (ROC) curve analysis was conducted to determine the diagnostic value of TUG1 in PCOS. TUG1 expression was also silenced in KGN cells to explore the role of TUG1 in cellular proliferation, apoptosis, cell-cycle progression, autophagy, and steroidogenesis. We found that TUG1 levels were dramatically increased in the PCOS group compared with those of the control group; this increased expression was related to a rising antral follicle count (R = 0.209, P < 0.001 versus control). The ROC curve indicated a significant separation between PCOS group and the control group (AUC: 0.702; 95% CI: 0.630–0.773; P < 0.001). TUG1 showed a predominantly nuclear localization in human GCs. TUG1 knockdown reduced cellular proliferation, and promoted MAPKs pathway-dependent apoptosis and P21-dependent autophagy, but may not affect cell-cycle progression. TUG1 knockdown increased aromatase expression and oestradiol biosynthesis. Our results indicate that increased TUG1 expression in PCOS GCs may contribute to excessive follicular activation and growth, and may disrupt the selection of dominant follicle. Our study shows that TUG1 can be used as a diagnostic biomarker for PCOS.

 抽象的

多囊卵巢综合征（PCOS）会导致育龄妇女无排卵性不孕，但 PCOS 的发病机制尚未确定。牛磺酸上调1 ( TUG1 ) 是一种进化上保守的长链非编码RNA，具有多种生物学功能；然而， TUG1在 PCOS 中的作用仍不清楚。在此，我们对 100 名 PCOS 患者和 100 名对照参与者的颗粒细胞 (GC) 中的TUG1表达进行了测定。进行受试者工作特征（ROC）曲线分析以确定TUG1对 PCOS 的诊断价值。 KGN 细胞中TUG1 的表达也被沉默，以探索TUG1在细胞增殖、凋亡、细胞周期进程、自噬和类固醇生成中的作用。我们发现，与对照组相比，PCOS 组的TUG1水平显着升高；这种表达增加与窦卵泡计数增加有关（与对照相比，R = 0.209，P < 0.001）。 ROC曲线表明PCOS组和对照组之间存在显着差异（AUC：0.702；95% CI：0.630–0.773；P< 0.001）。 TUG1在人类 GC 中显示出主要的核定位。 TUG1敲低可减少细胞增殖，促进 MAPKs 通路依赖性细胞凋亡和 P21 依赖性自噬，但可能不会影响细胞周期进程。 TUG1敲低增加了芳香酶表达和雌二醇生物合成。我们的结果表明，PCOS GC 中TUG1表达增加可能导致卵泡过度激活和生长，并可能破坏优势卵泡的选择。 我们的研究表明TUG1可用作 PCOS 的诊断生物标志物。