hsa_circRNA_BECN1 acts as a ceRNA to promote polycystic ovary syndrome progression by sponging the miR-619-5p/Rab5b axis.

IF 3.6 2区 医学 Q2 DEVELOPMENTAL BIOLOGY Molecular human reproduction Pub Date : 2023-11-01 DOI:10.1093/molehr/gaad036
Hairui Fan, Dongjie Zhou, Xiaomei Zhang, Min Jiang, Xiang Kong, Tongmin Xue, Lingling Gao, Dan Lu, Chenyue Tao, Liping Wang
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Abstract

Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease that affects women of reproductive age. It is also a significant cause of infertility. Circular RNAs have been found to have a crucial role in the development and progression of reproductive system diseases. In this study, we focused on circ_BECN1 and aimed to investigate its role and mechanism in PCOS, providing a foundation for early diagnosis and treatment of this condition. Our findings revealed an upregulation of circ_BECN1 expression in the ovarian granulosa cells (GCs) of PCOS patients. Additionally, the silencing of circ_BECN1 resulted in inhibited proliferation and enhanced apoptosis of the human ovarian granulosa-like tumor cell line (KGN), therefore implicating circ_BECN1 in the cell cycle process. Through a dual-luciferase reporting assay, we determined that circ_BECN1 acts as a sponge for miR-619-5p and that Rab5b is the target gene of miR-619-5p. Moreover, the expression of Rab5b was found to be upregulated in the ovarian tissue of PCOS patients. Knocking down circ_BECN1 resulted in decreased Rab5b expression, which was then restored by using a miR-619-5p inhibitor. Additionally, rescue experiments demonstrated that overexpressing Rab5b reversed the effects of circ_BECN1 knockdown on cell proliferation and apoptosis in KGN cells. In summary, our findings indicate that circ_BECN1 is upregulated in PCOS GCs and promotes cell growth and cell cycle progression, and reduces cell apoptosis by modulating the miR-619-5p/Rab5b axis. Therefore, circ_BECN1 may serve as a potential therapeutic target for PCOS treatment.

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Hsa_cirRNA_BECN1作为ceRNA通过吸收miR-619-5p/Rab5b轴来促进多囊卵巢综合征的进展。
多囊卵巢综合征(PCOS)是一种常见的生殖内分泌疾病,影响育龄妇女。它也是不育的重要原因。环状RNA(CircRNA)已被发现在生殖系统疾病的发展和进展中起着至关重要的作用。在本研究中,我们重点研究了circ_BECN1,旨在探讨其在多囊卵巢综合征中的作用和机制,为该疾病的早期诊断和治疗提供基础。我们的研究结果显示,多囊卵巢综合征患者卵巢颗粒细胞(GC)中circ_BECN1的表达上调。此外,circ_BECN1的沉默导致人类卵巢颗粒样肿瘤细胞系(KGN)的增殖抑制和细胞凋亡增强,因此circ_BEC21参与细胞周期过程。通过双荧光素酶报告测定,我们确定circ_BECN1充当miR-619-5p的海绵,并且Rab5b是miR-619-5 p的靶基因。此外,发现Rab5b的表达在多囊卵巢综合征患者的卵巢组织中上调。敲除circ_BECN1导致Rab5b表达降低,然后通过使用miR-619-5p抑制剂恢复Rab5b的表达。此外,拯救实验表明,过表达Rab5b逆转了circ_BECN1敲低对KGN细胞增殖和凋亡的影响。总之,我们的研究结果表明,circ_BECN1在PCOS GC中上调,并通过调节miR-619-5p/Rab5b轴促进细胞生长和细胞周期进展,减少细胞凋亡。因此,circ_BECN1可能成为PCOS治疗的潜在治疗靶点。
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来源期刊
Molecular human reproduction
Molecular human reproduction 生物-发育生物学
CiteScore
8.30
自引率
0.00%
发文量
37
审稿时长
6-12 weeks
期刊介绍: MHR publishes original research reports, commentaries and reviews on topics in the basic science of reproduction, including: reproductive tract physiology and pathology; gonad function and gametogenesis; fertilization; embryo development; implantation; and pregnancy and parturition. Irrespective of the study subject, research papers should have a mechanistic aspect.
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