Downregulation of lncRNA ZFAS1 and upregulation of microRNA-129 repress endocrine disturbance, increase proliferation and inhibit apoptosis of ovarian granulosa cells in polycystic ovarian syndrome by downregulating HMGB1.

The objective was to find the role of long-non-coding RNA zinc finger antisense 1 (lncRNA ZFAS1)/microRNA (miR)-129/high-mobility group box protein 1 (HMGB1) axis in polycystic ovary syndrome (PCOS). Ovarian granulosa cells from non-PCOS patients and PCOS patients were collected, and HMGB1, miR-129 and lncRNA ZFAS1 expression were detected. Ovarian granulosa cells were transfected with si-ZFAS1 or miR-129 mimics to verify their roles in P4 and E2 secretion, and the biological functions of ovarian granulosa cells. LncRNA ZFAS1 and HMGB1 were elevated, while miR-129 was down-regulated in ovarian granulosa cells of PCOS patients. Down-regulated lncRNA ZFAS1 or overexpressed miR-129 could decrease HMGB1 expression, increase P4 and E2 secretion, promote proliferation activity while inhibit apoptosis of ovarian granulosa cells in PCOS. LncRNA ZFAS1 could bind to miR-129 to promote HMGB1 expression, thereby affecting the endocrine disturbance, proliferation and apoptosis of ovarian granulosa cells in PCOS.

Zhu HL ，Chen YQ ，Zhang ZF 《-》

Downregulating lncRNA NEAT1 induces proliferation and represses apoptosis of ovarian granulosa cells in polycystic ovary syndrome via microRNA-381/IGF1 axis.

Researchers have revealed the combined functions of long noncoding RNAs (lncRNAs) and microRNA (miRNAs) in polycystic ovary syndrome (PCOS). This study aimed to understand the role of nuclear-enriched abundant transcript 1 (NEAT1) and miR-381 involving insulin-like growth factor 1 (IGF1) in PCOS. PCOS rat model was established by dehydroepiandrosterone induction. NEAT1, miR-381 and IGF1 expression in ovarian granulosa cells of PCOS patients and ovarian tissues of PCOS rats were tested. Bioinformatics website and dual luciferase reporter gene assay were utilized to verify the relationship between NEAT1 and miR-381 and that between miR-381 and IGF1. Levels of sex hormone, pathological changes and ovarian granulosa cell apoptosis in ovarian tissues of PCOS rats were detected. Ovarian granulosa cell proliferation and apoptosis were analyzed in vitro. NEAT1 and IGF1 expression increased while miR-381 expression decreased in the ovarian granulosa cells of patients with PCOS and the ovarian tissues of PCOS rats. In in vivo experiments, interference with NEAT1 improved the levels of sex hormones, alleviated pathological changes and suppressed ovarian granulosa cell apoptosis in the ovarian tissues of PCOS rats. In in vitro cell experiments, interference with NEAT1 suppressed apoptosis and enhanced cell proliferation of ovarian granulosa cells. NEAT1 interference-mediated effect would be reversed by up-regulating miR-381. NEAT1 acted as a ceRNA to adsorb miR-381 to target IGF1. Overexpression of IGF1 reversed the inhibitory effect of miR-381 on ovarian granulosa cell apoptosis. Interference with NEAT1 increases miR-381 and reduces IGF1 levels, effectively improving the levels of sex hormones and reducing the pathological damage of ovarian tissue in rats with PCOS.

Zhen J ，Li J ，Li X ，Wang X ，Xiao Y ，Sun Z ，Yu Q ... -  《-》

Down-regulated lncRNA HOTAIR alleviates polycystic ovaries syndrome in rats by reducing expression of insulin-like growth factor 1 via microRNA-130a.

It has been found that long noncoding RNA HOTAIR, microRNA-130a (miR-130a) and insulin-like growth factor 1 (IGF1) expression are associated with ovarian cancer, thus, we hypothesised that the HOTAIR/miR-130a/IGF1 axis might associate with endocrine disorders and biological behaviours of ovarian granulosa cells in rat models of polycystic ovary syndrome (PCOS). PCOS rat models were established by injection of dehydro-isoandrosterone, followed by treatment of si-HOTAIR, oe-HOTAIR, miR-130a mimics or miR-130a inhibitors. Serum hormonal levels were determined to evaluate endocrine conditions. The effect of HOTAIR and miR-130a on activities of isolated ovarian granulosa cells was assessed, as well as the involvement of IGF1.In the ovarian tissues and granulosa cells of PCOS rat models, highly expressed HOTAIR and IGF1 and poorly expressed miR-130a were identified. In response to oe-HOTAIR, serum levels of E2 , T and LH were increased and serum levels of FSH were reduced; the proliferation of granulosa cells was reduced and apoptosis was promoted; notably, expression of miR-130a was reduced while expression of IGF1 was increased. The treatment of si-HOTAIR reversed the situation. Furthermore, the binding of HOTAIR to miR-130a and targeting relationship of miR-130a and IGF1 were confirmed. LncRNA HOTAIR up-regulates the expression of IGF1 and aggravates the endocrine disorders and granulosa cell apoptosis through competitive binding to miR-130a in rat models of PCOS. Based on our finding, we predict that competitive binding of HOTAIR to miR-130a may act as a novel target for the molecular treatment of PCOS.

Jiang B ，Xue M ，Xu D ，Song J ，Zhu S ... -  《-》

Upregulation of microRNA-204 improves insulin resistance of polycystic ovarian syndrome via inhibition of HMGB1 and the inactivation of the TLR4/NF-κB pathway.

Jiang B ，Xue M ，Xu D ，Song Y ，Zhu S ... -  《-》

Down-regulation of MALAT1 aggravates polycystic ovary syndrome by regulating MiR-302d-3p-mediated leukemia inhibitory factor activity.

Accumulating evidence have shown the important roles of long noncoding RNA (lncRNA) in controlling different diseases. In the present study, we tried to explore the role which lncRNA MALAT1 plays in polycystic ovary syndrome (PCOS) with the involvement of microRNA-302d-3p (miR-302d-3p) and leukemia inhibitory factor (LIF). A PCOS rat model was established and characterized, followed by treatment with si-MALAT1, oe-MALAT1, miR-302d-3p mimic, or miR-302d-3p inhibitor constructs. Serum hormonal levels were detected to evaluate endocrine conditions. The effect of MALAT1 and miR-302d-3p on activities of ovarian granulosa cells was assessed, as well as the involvement of LIF. MALAT1 expression was shown to be downregulated in ovarian tissue of PCOS rats. Overexpression of MALAT1 in vitro promoted proliferation and inhibited apoptosis of ovarian granulosa cells. Overexpression of MALAT1 in vivo reduced the ovarian tissue injury and endocrine disorders accompanied with decreased level of FSH and elevated serum levels of E2, T, and LH in the PCOS rat. Overexpression of MALAT1 also promoted the expression of LIF, which could be reversed by overexpression of miR-302d-3p, indicating that MALAT1 up-regulated the expression of LIF via miR-302d-3p. Furthermore, overexpression of MALAT1 reduced endocrine disorders and ovarian tissue damage via the miR-302d-3p/LIF axis. Our study highlighted that MALAT1 plays a protective role in reducing ovarian tissue damage and endocrine disorder in PCOS by regulating the miR-302d-3p/LIF axis.

Chen Y ，Chen Y ，Cui X ，He Q ，Li H ... -  《-》