Long non-coding RNATUG1and its molecular mechanisms in polycystic ovary syndrome
Long non-coding RNATUG1and its molecular mechanisms in polycystic ovary syndrome
复制标题
长链非编码RNATUG1及其在多囊卵巢综合征中的分子机制
DOI：
10.1080/15476286.2020.1783850
复制
发表时间：
2020
期刊：
影响因子：
4.1
通讯作者：
Chen Shi-Ling
中科院分区：
文献类型：
--
作者：
Li Ying;Zhang Jun;Liu Yu-Dong;Zhou Xing-Yu;Chen Xin;Zhe Jing;Zhang Qing-Yan;Zhang Xiao-Fei;Chen Ying-Xue;Wang Zhe;Chen Shi-Ling
多囊卵巢综合征（PCOS）是育龄妇女无排卵性不孕的主要原因，但其发病机制尚不清楚。牛磺酸上调蛋白1（TUG 1）是一种进化上保守的长链非编码RNA，具有多种生物学功能，但TUG 1在PCOS中的作用尚不清楚。本文检测了100例PCOS患者和100例对照组的颗粒细胞（GC）中TUG 1的表达。通过受试者工作特征（ROC）曲线分析TUG 1在PCOS中的诊断价值，并通过沉默KGN细胞中TUG 1的表达，探讨TUG 1在细胞增殖、凋亡、细胞周期进程、自噬和类固醇合成中的作用。我们发现PCOS组中TUG 1的表达水平明显高于对照组，这种表达的增加与窦卵泡数的增加有关（R = 0.209，P < 0.001）。ROC曲线显示PCOS组与对照组有显著性差异（AUC：0.702; 95% CI：0.630-0.773; TUG 1在人胃癌细胞中主要定位于核内，TUG 1基因敲低可抑制胃癌细胞增殖，促进MAPKs途径依赖的凋亡和P21依赖的自噬，但可能不影响细胞周期进程。TUG 1敲低增加芳香化酶表达和雌二醇生物合成。我们的研究结果表明，PCOS GC中TUG 1表达的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TUG 1可以作为PCOS的诊断生物标志物。
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 ofTUG1in PCOS remains unclear. Herein,TUG1expression 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 ofTUG1in PCOS.TUG1expression was also silenced in KGN cells to explore the role ofTUG1in cellular proliferation, apoptosis, cell-cycle progression, autophagy, and steroidogenesis. We found thatTUG1levels 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).TUG1showed a predominantly nuclear localization in human GCs.TUG1knockdown reduced cellular proliferation, and promoted MAPKs pathway-dependent apoptosis and P21-dependent autophagy, but may not affect cell-cycle progression.TUG1knockdown increased aromatase expression and oestradiol biosynthesis. Our results indicate that increasedTUG1expression in PCOS GCs may contribute to excessive follicular activation and growth, and may disrupt the selection of dominant follicle. Our study shows thatTUG1can be used as a diagnostic biomarker for PCOS.