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环状 RNA 0001495 通过 miRNA-34c-5p/E2F3 轴影响子宫内膜异位症的发展。

Circ_0001495 influences the development of endometriosis through the miRNA-34c-5p/E2F3 axis.

机构信息

Anhui Medical University, Hefei, Anhui 230032, China; Department of Gynaecology, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui 241000, China; Department of Gynaecology, The First People's Hospital of Wuhu, Wuhu, Anhui 241000, China.

Department of Gynaecology, The First People's Hospital of Wuhu, Wuhu, Anhui 241000, China.

出版信息

Reprod Biol. 2024 Jun;24(2):100876. doi: 10.1016/j.repbio.2024.100876. Epub 2024 Mar 7.

DOI:10.1016/j.repbio.2024.100876
PMID:38458026
Abstract

Endometriosis is a chronic gynecological condition characterized by the presence of endometrial glands and stroma outside the uterine cavity., accounting for 7% of all female malignant tumors and 20%- 30% of malignant tumors of the female reproductive system. Multiple studies have shown that circular RNA (circRNA) has the potential to become a targeted target and marker for EM. However, the roles of circ_0001495 in EM are still unclear. Our research aims to reveal the molecular mechanism of circ_0001495 in EM. In this study, RT-PCR or western blot were conducted to determine mRNA and protein expression. cell viability, proliferation, migration, invasion, and apoptosis were assessed by CCK-8, EdU, wound healing, transwell, and flow cytometry analyses, respectively. Additionally, the targeting relationship between miR-34c-5p and circ_0001495 or E2F3 was confirmed through dual-luciferase reporter gene assay. We found significant overexpression of circ_0001495 in EM tissues and cells. Knockdown of circ_0001495 inhibited the proliferation, migration and invasion of ectopic endometrial stromal cells (EESCs) and increased cell apoptosis. Moreover, we found that circ_0001495 regulated E2F3 levels by interacting with miR-34c-5p in EESC. Furthermore, in vitro, miR-34c-5p inhibition or E2F3 overexpression could attenuate the effect of circ_0001495 silencing on EM progression. In addition, the vivo experiment demonstrated that inhibition of circ_0001495 could repress the development of endometriosis by regulating the miR-34c-5p/E2F3 axis. In conclusion, our study suggested that circ_0001495 promoted EM progression in vitro and in vivo through the miR-34c-5p/E2F3 axis, which might be a potential therapeutic target for EM.

摘要

子宫内膜异位症是一种慢性妇科疾病,其特征是子宫内膜腺体和基质出现在子宫腔外。它占所有女性恶性肿瘤的 7%,占女性生殖系统恶性肿瘤的 20%-30%。多项研究表明,环状 RNA (circRNA) 有可能成为子宫内膜异位症的靶向治疗靶点和标志物。然而,circ_0001495 在子宫内膜异位症中的作用尚不清楚。我们的研究旨在揭示 circ_0001495 在子宫内膜异位症中的分子机制。在这项研究中,通过 RT-PCR 或 Western blot 测定 mRNA 和蛋白表达。通过 CCK-8、EdU、划痕愈合、transwell 和流式细胞术分析分别评估细胞活力、增殖、迁移、侵袭和凋亡。此外,通过双荧光素酶报告基因检测证实了 miR-34c-5p 与 circ_0001495 或 E2F3 的靶向关系。我们发现 circ_0001495 在子宫内膜异位症组织和细胞中表达显著上调。circ_0001495 敲低抑制异位子宫内膜基质细胞 (EESCs) 的增殖、迁移和侵袭,并增加细胞凋亡。此外,我们发现 circ_0001495 通过与 miR-34c-5p 相互作用调节 EESC 中的 E2F3 水平。此外,在体外,miR-34c-5p 抑制或 E2F3 过表达可以减弱 circ_0001495 沉默对子宫内膜异位症进展的影响。此外,体内实验表明,通过调节 miR-34c-5p/E2F3 轴,抑制 circ_0001495 可以抑制子宫内膜异位症的发展。总之,我们的研究表明,circ_0001495 通过 miR-34c-5p/E2F3 轴在体内外促进子宫内膜异位症的进展,这可能是子宫内膜异位症的潜在治疗靶点。

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