miR-323-3p regulates the steroidogenesis and cell apoptosis in polycystic ovary syndrome (PCOS) by targeting IGF-1
miR-323-3p regulates the steroidogenesis and cell apoptosis in polycystic ovary syndrome (PCOS) by targeting IGF-1
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miR-323-3p 通过靶向 IGF-1 调节多囊卵巢综合征 (PCOS) 中的类固醇生成和细胞凋亡
DOI：
10.1016/j.gene.2018.10.006
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发表时间：
2019-01-30
期刊：
影响因子：
3.5
通讯作者：
Cao, Yunxia
中科院分区：
文献类型：
--
作者：
Wang, Tianjuan;Liu, Yajing;Cao, Yunxia
多囊卵巢综合征（PCOS）是一种内分泌和代谢异质性疾病。在育龄妇女中发病率达到5%至10%。卵泡发育异常被认为是PCOS的共同特征，但其病因和发病机制尚不清楚。已有研究证明microRNA的异常调节与PCOS的发病有关。在本研究中，我们研究了miR-323- 3 p对人卵丘细胞（CC）的影响。我们还研究了miR-323- 3 p对人粒层细胞样肿瘤细胞系（KGN）或通过用二氢睾酮（DHT）刺激的原代人CC的潜在机制。我们的研究结果表明，与对照组相比，PCOS妇女的人类CC中miR-323- 3 p的水平下调。抑制miR-323- 3 p的表达可上调KGN细胞的类固醇合成，促进细胞凋亡。此外，我们的数据证实了胰岛素样生长因子1（IGF-1）基因是miR-3233 p的直接靶点。此外，miR-323- 3 p的模拟物抑制IGF-1的表达，从而下调AR、AMHR-II、CYP 19 A、EGFR和加塔-4的水平。结论：miR-323- 3 p靶向IGF-1调控CCs的类固醇合成和活性，在PCOS的发生发展中起重要作用。我们的研究结果表明，miR-323- 3 p是一个新的和有前途的分子靶点，用于改善PCOS中的CC功能障碍。
Polycystic ovary syndrome (PCOS) is an endocrine and metabolic heterogeneous disorder. The incidence of which reaches 5% to 10% among reproductive-age women. Abnormal folliculogenesis is considered to be a common characteristic of PCOS, but the cause of this disorder and its pathogenesis still remain uncertain. Previous studies had proved that dysregulation of microRNAs is related to the pathogenesis of PCOS. In this study, we investigated the effect of miR-323-3p on the human cumulus cells (CCs). We also investigated the underlying mechanisms of miR-323-3p on human granulosa-like tumor cell line (KGN) or primary human CCs by stimulating with Dihydrotestosterone (DHT). Our findings suggested that the level of miR-323-3p in human CCs of women with PCOS was down-regulated, compared with that of the control group. Moreover, the inhibition of the level of miR-323-3p could up-regulate of the steroidogenesis and promote the apoptosis in KGN cells. In addition, our data confirmed that the Insulin-like growth factor 1 (IGF-1) gene was the direct target of miR-3233p. Furthermore, the mimic of miR-323-3p inhibited the expression of IGF-1, which down-regulated the levels of AR, AMHR-II, CYP19A, EGFR, and GATA-4. In conclusion, miR-323-3p targeting IGF-1 regulates the steroidogenesis and the activity of CCs, which plays an important role in the occurrence and development of PCOS. Our results have shown that miR-323-3p is a novel and promising molecular target for the improvement of the dysfunction of CCs in PCOS.