CircAGFG1 Promotes Ovarian Cancer Progression Through the miR-409-3 p/ZEB1 Axis.

IF 2.7 4区 医学 Q3 ONCOLOGY Technology in Cancer Research & Treatment Pub Date : 2024-01-01 DOI:10.1177/15330338241252423
Jie Luo, Hua Zhong, Mei Guo, Peihong Xiao, Rongyu Cao, Mandan Zhao, Yongping Jing
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Abstract

Objectives: Circular RNAs (circRNAs) serve a crucial regulatory role in ovarian cancer (OC). Circular RNA ArfGAP with FG repeats 1 (circAGFG1) has been shown to be involved in promoting the progression of several cancers, containing triple-negative breast cancer, esophageal cancer and colorectal cancer. However, the function of circAGFG1 in OC is unclear.

Methods: Quantitative real-time reverse transcription PCR (RT-qPCR) was conducted to determine the expression levels of circAGFG1 and miR-409-3p. The proliferation and metastasis of cells were determined by colony formation assays, EdU assays, transwell assays and wound healing assays. In addition, a dual-luciferase reporter assay was performed to validate the mechanism between circAGFG1, miR-409-3p, and ZEB1.

Results: Our data suggested that circAGFG1 was significantly overexpressed in OC tissues compared to normal ovarian epithelial tissues. Overexpression of circAGFG1 was correlated with intraperitoneal metastasis, tumor recurrence and advanced stage. Additionally, circAGFG1 overexpression revealed a poor prognosis in OC patients. Knockdown of circAGFG1 suppressed the proliferation, invasion and migration of OC cells. Mechanistically, circAGFG1 acted as a sponge of miR-409-3p to enhance the expression level of zinc finger E-box binding homeobox 1 (ZEB1), thereby conferring OC cell proliferation, invasion and migration. Importantly, re-expression of ZEB1 effectively reversed the effects of circAGFG1 knockdown on OC cells.

Conclusions: In summary, our study indicated that circAGFG1 may act as a prognostic biomarker and potential therapeutic target for patients with OC.

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CircAGFG1 通过 miR-409-3 p/ZEB1 轴促进卵巢癌进展
目的:环状 RNA(circRNA)在卵巢癌(OC)中发挥着重要的调控作用。循环 RNA ArfGAP with FG repeats 1(circAGFG1)已被证明参与促进多种癌症的进展,包括三阴性乳腺癌、食管癌和结直肠癌。然而,circAGFG1在OC中的功能尚不清楚:方法:采用实时逆转录定量 PCR(RT-qPCR)检测 circAGFG1 和 miR-409-3p 的表达水平。通过集落形成试验、EdU 试验、透孔试验和伤口愈合试验测定细胞的增殖和转移。此外,还进行了双荧光素酶报告实验来验证 circAGFG1、miR-409-3p 和 ZEB1 之间的作用机制:结果:我们的数据表明,与正常卵巢上皮组织相比,circAGFG1在OC组织中明显过表达。circAGFG1的过表达与腹膜内转移、肿瘤复发和晚期相关。此外,circAGFG1的过表达还表明卵巢癌患者的预后较差。敲除circAGFG1可抑制OC细胞的增殖、侵袭和迁移。从机理上讲,circAGFG1可作为miR-409-3p的海绵,提高锌指E盒结合同源框1(ZEB1)的表达水平,从而促进OC细胞的增殖、侵袭和迁移。重要的是,ZEB1的重新表达能有效逆转circAGFG1敲除对OC细胞的影响:综上所述,我们的研究表明,circAGFG1可作为OC患者的预后生物标志物和潜在治疗靶点。
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来源期刊
CiteScore
4.40
自引率
0.00%
发文量
202
审稿时长
2 months
期刊介绍: Technology in Cancer Research & Treatment (TCRT) is a JCR-ranked, broad-spectrum, open access, peer-reviewed publication whose aim is to provide researchers and clinicians with a platform to share and discuss developments in the prevention, diagnosis, treatment, and monitoring of cancer.
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