miR-483 is Down-Regulated in Polycystic Ovarian Syndrome and Inhibits KGN Cell Proliferation via Targeting Insulin-Like Growth Factor 1 (IGF1).

miR-483 is Down-Regulated in Polycystic Ovarian Syndrome and Inhibits KGN Cell Proliferation via Targeting Insulin-Like Growth Factor 1 (IGF1).
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DOI:
10.12659/msm.897301
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发表时间:
2016-09-23
期刊:
Medical science monitor : international medical journal of experimental and clinical research
影响因子:
--
通讯作者:
Tan L
Tan L
中科院分区:
其他
文献类型:
--
作者:
Xiang Y;Song Y;Li Y;Zhao D;Ma L;Tan L

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多囊卵巢综合征(PCOS)是绝经前女性常见的代谢性疾病,其特征是雄激素过多症、少排卵和胰岛素抵抗。 microRNA 在调节 PCOS 的关键因素中发挥着关键作用。然而,相关研究仍然有限。本研究旨在揭示miR-483在PCOS中的作用和潜在机制。招募 PCOS 患者 (n=20) 检测病变和正常卵巢皮质中 miR-483 的表达。使用人颗粒样肿瘤细胞系 KGN 通过细胞转染改变 miR-483 表达。采用MTT法和集落形成法分析细胞活力和增殖情况,流式细胞术检测细胞周期。通过荧光素酶报告基因测定验证了 miR-483 和 IGF1 之间的相互作用。 KGN细胞进一步用胰岛素处理,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 显着下调(P<0.001)。在 KGN 细胞中,miR-483 的过度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海绵诱导了相反的效果。 miR-483直接靶向IGF1 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 是一种 PCOS 抑制剂,可能通过靶向 IGF1 来抑制细胞增殖,并且它参与胰岛素诱导的细胞增殖。 miR-483 是诊断和治疗 PCOS 的潜在替代方案。
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. 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. 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. 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.
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