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lncRNA PVT1/MicroRNA-17-5p/PTEN Axis Regulates Secretion of E2 and P4, Proliferation, and Apoptosis of Ovarian Granulosa Cells in PCOS.
Molecular Therapy - Nucleic Acids ( IF 8.8 ) Pub Date : 2020-02-13 , DOI: 10.1016/j.omtn.2020.02.007
Gelin Liu 1 , Shengxian Liu 1 , Guanlin Xing 1 , Fang Wang 1
Affiliation  

Recently, the roles of microRNAs (miRNAs) and long non-coding RNAs (lncRNAs) were identified in polycystic ovary syndrome (PCOS). In the present study, we investigated the role of the lncRNA PVT1/miR-17-5p/PTEN axis in PCOS ovarian granulosa cells. Expression of PVT1, miR-17-5p and PTEN in PCOS ovarian granulosa cells and follicular fluid was detected, and homeostatic model assessment of insulin resistance (HOMA-IR) and the levels of fasting plasma glucose (FPG), fasting insulin (FINS), and sex hormones were assessed. Then, the proliferation, apoptosis, and colony formation ability of ovarian granulosa cells were evaluated. The binding relationship between PVT1 and miR-17-5p as well as the target relationship between miR-17-5p and PTEN were determined by bioinformatics analysis, luciferase activity assay, RNA-induced silencing complex assay, and RNA pull-down assay. The levels of sex hormone-binding globulin and follicle-stimulating hormone were abated and the levels of luteinizing hormone, testosterone, FINS, FPG, and HOMA-IR were increased in PCOS serum. PVT1 and PTEN were overexpressed and miR-17-5p was reduced in PCOS ovarian granulosa cells and follicular fluid. Overexpressed miR-17-5p and inhibited PVT1 could decelerate apoptosis while accelerating colony formation ability and proliferation of ovarian granulosa cells in PCOS. Moreover, overexpression of PVT1 and reduced miR-17-5p could reverse these results. There existed target relation among PVT1, miR-17-5p, and PTEN, and PVT1 could inhibit miR-17-5p, thereby elevating PTEN. Our study suggests that inhibited PVT1 and overexpressed miR-17-5p result in downregulation of PTEN and promotion of cell proliferation, as well as inhibition of apoptosis of ovarian granulosa cells in PCOS.



中文翻译:

lncRNA PVT1/MicroRNA-17-5p/PTEN Axis 调节 PCOS 中卵巢颗粒细胞 E2 和 P4 的分泌、增殖和凋亡。

最近,在多囊卵巢综合征 (PCOS) 中发现了 microRNA (miRNA) 和长链非编码 RNA (lncRNA) 的作用。在本研究中,我们研究了 lncRNA PVT1/miR-17-5p/PTEN 轴在 PCOS 卵巢颗粒细胞中的作用。检测PCOS卵巢颗粒细胞和卵泡液中PVT1、miR-17-5p和PTEN的表达,并进行胰岛素抵抗(HOMA-IR)和空腹血糖(FPG)、空腹胰岛素(FINS)水平的稳态模型评估和性激素进行了评估。然后,评估卵巢颗粒细胞的增殖、凋亡和集落形成能力。通过生物信息学分析、荧光素酶活性测定、RNA诱导沉默复合物测定、和 RNA 下拉分析。PCOS血清中性激素结合球蛋白和促卵泡激素水平降低,促黄体生成素、睾酮、FINS、FPG和HOMA-IR水平升高。PVT1 和 PTEN 在 PCOS 卵巢颗粒细胞和卵泡液中过表达,miR-17-5p 减少。过表达 miR-17-5p 和抑制 PVT1 可以减缓 PCOS 中卵巢颗粒细胞的集落形成能力和增殖能力。此外,PVT1 的过表达和减少的 miR-17-5p 可以逆转这些结果。PVT1、miR-17-5p和PTEN之间存在靶点关系,PVT1可以抑制miR-17-5p,从而提高PTEN。我们的研究表明,抑制 PVT1 和过表达 miR-17-5p 导致 PTEN 下调和促进细胞增殖,

更新日期:2020-02-13
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