Abstract
ObjectiveResearchers 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.MethodsPCOS 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.ResultsNEAT1 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.ConclusionInterference 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.
Highlights
Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease that is often characterized by increased dehydroepiandrosterone (DHEA) [1, 2]
nuclear-enriched abundant transcript 1 (NEAT1) (Fig. 1A), miR-381 (Fig. 1B) and Insulin-like growth factor 1 (IGF1) (Fig. 1C–E) expression in ovarian granulosa cells of patients with PCOS was measured by RT-qPCR and Western blot analysis, and the results revealed that IGF1 and NEAT1 expression was increased and miR-381 expression was decreased in the PCOS group versus the non-PCOS group
To explore the mechanism of NEAT1/miR-381/IGF1 axis in PCOS, we applied Pearson test to analyze the relationship between NEAT1 and miR-381 expression, as well as that between miR-381 and IGF1 expression in PCOS, and the results showed (Fig. 1F, G) that in ovarian granulosa cells of patients with PCOS, NEAT1 expression was negatively correlated with miR-381 expression (r = − 0.68, P < 0.01), and miR-381 expression was negatively correlated with IGF1 expression (r = − 0.73, P < 0.01)
Summary
Polycystic ovary syndrome (PCOS) is a reproductive endocrine disease that is often characterized by increased dehydroepiandrosterone (DHEA) [1, 2]. NEAT1 has the ability to promote ovarian granulosa cell proliferation and suppress apoptosis through acting as a sponge of microRNAs (miRNAs) [9]. Repressed miR-129 expression could induce endocrine disturbance, suppress proliferation and enhance apoptosis of ovarian granulosa cells in PCOS [11]. IGF1 is one of the highly expressed genes in PCOS that contribute to the aggravated endocrine disorder and granulosa cell apoptosis [13]. Another study has revealed that the concentration of IGF1 is high in follicular fluid of patients with PCOS [15]. The potential mechanism of NEAT1/miR-381/IGF1 axis in PCOS has not been explored yet. This research was determined to grasp the mechanism of NEAT1 in ovarian granulosa cell proliferation and apoptosis with the involvement of miR-381 and IGF1 in PCOS
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