miR-34a-5p modulation of polycystic ovary syndrome via targeting the NOTCH signaling pathway.

IF 3.8 3区 医学 Q1 REPRODUCTIVE BIOLOGY
Kexin Zhang, Xiaomeng Wang, Fang Liu, Hong Lin, Yan Wang, Min Zhao, Xiaofei Wang, Yijing Chu, Lin Xu
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Abstract

Purpose: Polycystic ovary syndrome (PCOS) is currently recognized as a condition that affects several systems in the body, including the reproductive, endocrine, and cardiovascular systems. Prevalent among teenagers and women of reproductive age. Prior research has demonstrated an elevation of miR-34a-5p within the follicular fluid (FF) of women of PCOS. Despite this, the precise mechanisms through which miR-34a-5p influences granulosa cells (GC) development and function remain poorly characterized.

Methods: Therefore, this study investigates the involvement and pathogenic mechanisms of miR-34a-5p within GCs in the context of PCOS. The human granulosa-like tumor cell line (KGN) got transfected at a control, as well as a miR-34a-5p mimic and inhibitor, respectively. Monitor cellular proliferation in each experimental group. The experimental methods included RT-qPCR, CCK8, flow cytometry and western blotting. Also, the interaction between miR-34a-5p and the particular sequence of JAG1 has been verified using the dual luciferase assay. Further investigation of the connection involving miR-34a-5p and the Notch signaling pathway was conducted using bioinformatics analysis and experimental methods.

Results: The results demonstrated that miR-34a-5p expression was significantly elevated in the serum(p<0. 0001)and FF (p = 0. 0402) of PCOS, whereas its expression in GCs (p = 0. 5522) showed no significant variation. Overexpressing miR-34a-5p caused a decrease in the rate at which KGN cells multiplied and an increase in programmed cell death. Conversely, inhibiting miR-34a-5p resulted in an increase in cell growth and a decrease in programmed cell death. Bioinformatics analysis and experimental results further demonstrated thatmiR-34a-5p interacts with the 3'UTR region of JAG1, leading to a negative regulation of the Jagged1-Notch signaling pathway.

Conclusion: In summary, the miR-34a-5p molecule inhibits the growth of GCs as well as triggers programmed cell death by regulating the Jagged1-Notch signaling pathway. Silencing miR-34a-5p prevents dysfunction in GCs. Our analysis implies that miR-34a-5p is a new molecular site to treat PCOS.

目的:多囊卵巢综合征(PCOS)目前被认为是一种影响人体多个系统的疾病,包括生殖系统、内分泌系统和心血管系统。多发于青少年和育龄妇女。先前的研究表明,多囊卵巢综合症女性卵泡液(FF)中的 miR-34a-5p 会升高。尽管如此,miR-34a-5p 影响颗粒细胞(GC)发育和功能的确切机制仍鲜为人知:因此,本研究探讨了 miR-34a-5p 在多囊卵巢综合征背景下参与 GC 的作用及其致病机制。人肉芽肿样肿瘤细胞系(KGN)分别转染对照组、miR-34a-5p模拟物和抑制剂。监测各实验组的细胞增殖情况。实验方法包括 RT-qPCR、CCK8、流式细胞术和免疫印迹。此外,还利用双荧光素酶试验验证了 miR-34a-5p 与 JAG1 特定序列之间的相互作用。通过生物信息学分析和实验方法,进一步研究了 miR-34a-5p 与 Notch 信号通路的联系:结果表明,miR-34a-5p 在血清(p)中的表达显著升高:综上所述,miR-34a-5p分子通过调节Jagged1-Notch信号通路抑制GCs的生长并引发细胞程序性死亡。沉默 miR-34a-5p 可防止 GCs 功能障碍。我们的分析表明,miR-34a-5p 是治疗多囊卵巢综合症的一个新分子位点。
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来源期刊
Journal of Ovarian Research
Journal of Ovarian Research REPRODUCTIVE BIOLOGY-
CiteScore
6.20
自引率
2.50%
发文量
125
审稿时长
>12 weeks
期刊介绍: Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ. Topical areas include, but are not restricted to: Ovary development, hormone secretion and regulation Follicle growth and ovulation Infertility and Polycystic ovarian syndrome Regulation of pituitary and other biological functions by ovarian hormones Ovarian cancer, its prevention, diagnosis and treatment Drug development and screening Role of stem cells in ovary development and function.
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