Xiang Yungai, Song Yuxia, Li Yan, Zhao Dongmei, Ma Liying, Tan Li
Department of Reproductive Medicine, The Second Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China (mainland).
Med Sci Monit. 2016 Sep 23;22:3383-3393. doi: 10.12659/msm.897301.
BACKGROUND Polycystic ovarian syndrome (PCOS) is a common metabolic disorder in premenopausal woman, characterized by hyperandrogenism, oligoanovulation, and insulin resistance. microRNAs play pivotal roles in regulating key factors of PCOS. However, relevant research remains limited. This study aimed to reveal the role and potential mechanism of miR-483 in PCOS. MATERIAL AND METHODS PCOS patients (n=20) were recruited for detecting miR-483 expression in lesion and normal ovary cortex. Human granulosa-like tumor cell line KGN was used to alter miR-483 expression by cell transfection. Cell viability and proliferation were analyzed by MTT assay and colony formation assay, and cell cycle was detected by flow cytometry. Interaction between miR-483 and IGF1 was verified by luciferase reporter assay. KGN cells were further treated by insulin to investigate the relationship between miR-483 and insulin. RESULTS miR-483 was significantly down-regulated in lesion ovary cortex from PCOS patients (P<0.001). In KGN cells, overexpression of miR-483 inhibited cell viability and proliferation, and induced cell cycle arrest. miR-483 also inhibited CCNB1, CCND1, and CDK2. miR-483 sponge induced the opposite effects. miR-483 directly targeted IGF1 3'UTR, and IGF1 promoted KGN cell proliferation and reversed miR-483-inhibited cell viability. Insulin treatment in KGN cells inhibited miR-483, and promoted IGF1 and cell proliferation. CONCLUSIONS These results suggest that miR-483 is a PCOS suppressor inhibiting cell proliferation, possibly via targeting IGF1, and that it is involved in insulin-induced cell proliferation. miR-483 is a potential alternative for diagnosing and treating PCOS.
多囊卵巢综合征(PCOS)是绝经前女性常见的代谢紊乱疾病,其特征为高雄激素血症、排卵稀少和胰岛素抵抗。微小RNA在调节PCOS的关键因素中起关键作用。然而,相关研究仍然有限。本研究旨在揭示miR-483在PCOS中的作用及潜在机制。
招募20例PCOS患者,检测病变卵巢和正常卵巢皮质中miR-483的表达。用人颗粒细胞样肿瘤细胞系KGN通过细胞转染改变miR-483表达。采用MTT法和集落形成试验分析细胞活力和增殖情况,通过流式细胞术检测细胞周期。通过荧光素酶报告基因试验验证miR-483与IGF1之间的相互作用。用胰岛素进一步处理KGN细胞,以研究miR-483与胰岛素之间的关系。
PCOS患者病变卵巢皮质中miR-483显著下调(P<0.001)。在KGN细胞中,miR-483过表达抑制细胞活力和增殖,并诱导细胞周期停滞。miR-483还抑制CCNB1、CCND1和CDK2。miR-483海绵体产生相反的作用。miR-483直接靶向IGF1的3'UTR,IGF1促进KGN细胞增殖并逆转miR-483抑制的细胞活力。KGN细胞中的胰岛素处理抑制miR-483,并促进IGF1和细胞增殖。
这些结果表明,miR-483可能通过靶向IGF1抑制细胞增殖,是PCOS的抑制因子,并且它参与胰岛素诱导的细胞增殖。miR-483是诊断和治疗PCOS的潜在替代物。