Circ_0007331 knock-down suppresses the progression of endometriosis via miR-200c-3p/HiF-1α axis.

IF 5.3 2区 医学 Q1 Biochemistry, Genetics and Molecular Biology Journal of Cellular and Molecular Medicine Pub Date : 2020-11-01 Epub Date: 2020-09-22 DOI:10.1111/jcmm.15833
Lan Dong, Lu Zhang, Hua Liu, Meiting Xie, Jing Gao, Xiaoyan Zhou, Qinghong Zhao, Silin Zhang, Jing Yang
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Abstract

Endometriosis is considered a benign gynaecological disease with cancer-like characterizations, which has a high incidence among women of reproductive age. However, this disease has so far lacked timely diagnosis and effective treatment owing to its unclear aetiology. In this study, we identified aberrant high expression of circ_0007331 in ectopic endometrial cells by comparing the endometrial samples from patients with and without endometriosis. Further functional experiments revealed that circ_0007331 knock-down effectively suppressed the viability, proliferation and invasive capacity of ectopic endometrial cells. Additionally, we attempted to define the molecular mechanism of circ_0007331 in the initiation and progression of endometriosis. Circ_0007331 acted as a miRNA sponge for miR-200c-3p to indirectly regulate the function of HIF-1α, which plays a key role in the local angiogenesis and hypoxic mechanisms of ectopic endometrium. A final in vivo experiment confirmed that circ_0007331 knock-down could suppress the development of endometriosis through down-regulating the expression of HIF-1α. Collectively, we preliminarily characterized the role and possible insights of circ_0007331/miR-200c-3p/HIF-1α axis in the proliferation and invasion of ectopic endometrial cells. We hope that by exploring the potential function and molecular mechanism of circ_0007331, we can increase our biological insight into the pathogenesis of endometriosis, which will bring the new ways for the diagnosis and therapy of this disease.

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通过 miR-200c-3p/HiF-1α 轴敲除 Circ_0007331 可抑制子宫内膜异位症的进展。
子宫内膜异位症被认为是一种具有类似癌症特征的良性妇科疾病,在育龄妇女中发病率很高。然而,由于病因不清,该病至今仍缺乏及时诊断和有效治疗。在这项研究中,我们通过比较子宫内膜异位症患者和非子宫内膜异位症患者的子宫内膜样本,发现了circ_0007331在异位子宫内膜细胞中的异常高表达。进一步的功能实验表明,敲除 circ_0007331 能有效抑制异位子宫内膜细胞的活力、增殖和侵袭能力。此外,我们还试图明确 circ_0007331 在子宫内膜异位症的发生和发展过程中的分子机制。Circ_0007331 充当了 miR-200c-3p 的 miRNA 海绵,间接调节 HIF-1α 的功能,而 HIF-1α 在异位子宫内膜局部血管生成和缺氧机制中起着关键作用。最后的体内实验证实,circ_0007331基因敲除可以通过下调HIF-1α的表达来抑制子宫内膜异位症的发展。综上所述,我们初步揭示了circ_0007331/miR-200c-3p/HIF-1α轴在异位子宫内膜细胞增殖和侵袭中的作用及可能的启示。我们希望通过探索circ_0007331的潜在功能和分子机制,提高我们对子宫内膜异位症发病机制的生物学认识,为该病的诊断和治疗提供新的思路。
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来源期刊
CiteScore
10.00
自引率
1.90%
发文量
496
审稿时长
28 weeks
期刊介绍: Bridging physiology and cellular medicine, and molecular biology and molecular therapeutics, Journal of Cellular and Molecular Medicine publishes basic research that furthers our understanding of the cellular and molecular mechanisms of disease and translational studies that convert this knowledge into therapeutic approaches.
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