LncRNA GAS5 is upregulated in polycystic ovary syndrome and regulates cell apoptosis and the expression of IL-6

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LncRNA GAS5 is upregulated in polycystic ovary syndrome and regulates cell apoptosis and the expression of IL-6 Chunxia Wang1, Shishi Yue2, Yaru Jiang2, Yanjia Mao2, Zhijing Zhao2, Xinwei Liu3, Xiaoqian Zhang3, Dongxu Pei3 and Yongwei Li3*

Abstract Background: GAS5 contains a hormone response element that can induce cell apoptosis in breast cancer. It is known that cell apoptosis and hormone response play crucial roles in polycystic ovary syndrome (PCOS), indicating the potential involvement of GAS5 in PCOS. This study was performed to investigate the potential involvement of GAS5 and IL-6 (a critical player in PCOS) in PCOS. Methods: Research subjects of this study included 60 PCOS patients and 60 healthy controls. The expression levels of GAS5 and IL-6 in plasma of both patients and controls were measured by qPCR and ELISA, respectively. Cell transfections were performed to analyze the interaction between GAS5 and IL-6. Cell apoptosis was analyzed by cell apoptosis assay. Results: GAS5 was upregulated in plasma of PCOS patients. The expression levels of GAS5 were positively correlated with the expression levels of IL-6. Altered expression levels of GAS5 and IL-6 distinguished PCOS patients from healthy controls. In cells of a granulosa-like tumor cell line (KGN), overexpression of GAS5 led to upregulated IL-6, while silencing of GAS5 played an opposite role. Cell apoptosis analysis showed that overexpression of GAS5 significantly decreased apoptosis rate of KGN cells. Silencing of GAS5 increased the rate of KGN cell apoptosis. Conclusions: GAS5 is upregulated in PCOS and regulates cell apoptosis and the expression of IL-6. Keywords: Polycystic ovary syndrome, GAS5, IL-6, Granulosa, Apoptosis

Background Polycystic ovary syndrome (PCOS) is a common type of endocrine and metabolic disorder that affects females at their reproductive age [1]. PCOS patients suffer from excess male hormone production and prolonged or infrequent menstrual periods [2]. The ovary of PCOS patients may not regularly release eggs due to the development of numerous small follicles [3]. Prevalence of PCOS varies across the world. It is generally believed that about * Correspondence: [email protected] 3 Department of Clinical Laboratory, The Second Affiliated Hospital of Henan University of TCM, No.6 Dongfeng Road, Henan Province 450002 Zhengzhou City, People’s Republic of China Full list of author information is available at the end of the article

5–20% of women suffer from PCOS before the end of reproductive age [4]. The development of PCOS is accompanied by altered cell behaviors, such as apoptosis, which not only causes infertility [5], but also increases the risk of metabolic disorders and cardiovascular disease [6]. Therefore, effective treatment of PCOS is critical. Studies on the molecular pathogenesis of PCOS have revealed a considerable number of genetic alterations involved in the pathogenesis of this disease [7, 8]. Functional characterization of genetic players may contribute to the development of nov