Long non-coding RNA <i>TUG1</i> and its molecular mechanisms in polycystic ovary syndrome

Polycystic ovary syndrome (PCOS) causes anovulatory infertility in women of reproductive age, but etiopathogenesis of PCOS remains undetermined. Taurine up-regulated 1 (<i>TUG1</i>), an evolutionarily conserved long non-coding RNA, performs various biological functions; however, the role of <i>TUG1</i> in PCOS remains unclear. Herein, <i>TUG1</i> 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 <i>TUG1</i> in PCOS. <i>TUG1</i> expression was also silenced in KGN cells to explore the role of <i>TUG1</i> in cellular proliferation, apoptosis, cell-cycle progression, autophagy, and steroidogenesis. We found that <i>TUG1</i> 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 &lt; 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 &lt; 0.001). <i>TUG1</i> showed a predominantly nuclear localization in human GCs. <i>TUG1</i> knockdown reduced cellular proliferation, and promoted MAPKs pathway-dependent apoptosis and P21-dependent autophagy, but may not affect cell-cycle progression. <i>TUG1</i> knockdown increased aromatase expression and oestradiol biosynthesis. Our results indicate that increased <i>TUG1</i> expression in PCOS GCs may contribute to excessive follicular activation and growth, and may disrupt the selection of dominant follicle. Our study shows that <i>TUG1</i> can be used as a diagnostic biomarker for PCOS.