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hsa_circRNA_BECN1 通过海绵吸附 miR-619-5p/Rab5b 轴促进多囊卵巢综合征进展。

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

机构信息

Key Laboratory for Animal Genetics, Breeding, Reproduction and Molecular Design, College of Animal Science and Technology, Yangzhou University, Yangzhou, China.

College of Veterinary Medicine, Yangzhou University, Yangzhou, China.

出版信息

Mol Hum Reprod. 2023 Nov 1;29(11). doi: 10.1093/molehr/gaad036.

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.

摘要

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。它也是不孕的一个重要原因。环状 RNA 已被发现在生殖系统疾病的发展和进展中起着关键作用。在这项研究中,我们专注于 circ_BECN1,并旨在研究其在 PCOS 中的作用和机制,为这种疾病的早期诊断和治疗提供基础。我们的研究结果表明,PCOS 患者的卵巢颗粒细胞(GC)中 circ_BECN1 的表达上调。此外,circ_BECN1 的沉默导致人卵巢颗粒样肿瘤细胞系(KGN)的增殖受到抑制和凋亡增强,因此暗示 circ_BECN1 参与细胞周期过程。通过双荧光素酶报告基因实验,我们确定 circ_BECN1 作为 miR-619-5p 的海绵,Rab5b 是 miR-619-5p 的靶基因。此外,在 PCOS 患者的卵巢组织中发现 Rab5b 的表达上调。敲低 circ_BECN1 导致 Rab5b 表达减少,而使用 miR-619-5p 抑制剂则可恢复 Rab5b 表达。此外,挽救实验表明,过表达 Rab5b 可逆转 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程,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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