Circ_0058058 Knockdown Inhibits Acute Myeloid Leukemia Progression by Sponging miR-4319 to Regulate EIF5A2 Expression.

IF 2.4 4区 医学 Q3 MEDICINE, RESEARCH & EXPERIMENTAL Cancer Biotherapy and Radiopharmaceuticals Pub Date : 2023-12-01 Epub Date: 2021-01-19 DOI:10.1089/cbr.2020.4170
Ting Zhang, Ying Zhou, Jun Guan, Hui Cheng
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引用次数: 8

Abstract

Background: Acute myeloid leukemia (AML) is the most common acute leukemia in adults. Circular RNAs (circRNAs) participate in the deterioration of many hominine cancers, including AML. In this study, the authors investigated the role and potential mechanism of circ_0058058 in AML progression. Methods: The expression of circ_0058058, microRNA-4319 (miR-4319), and eukaryotic initiation factor 5A2 (EIF5A2) was determined by quantitative real-time polymerase chain reaction. Cell proliferation, apoptosis, migration, and invasion were evaluated by cell counting kit-8 (CCK-8), cell colony formation, flow cytometry, and transwell assay, respectively. Levels of the relative proteins were detected by Western blot. The connection among circ_0058058, miR-4319, and EIF5A2 was verified by dual-luciferase reporter assay. Results: Circ_0058058 and EIF5A2 were enhanced, whereas miR-4319 was declined in AML. Circ_0058058 knockdown inhibited cell proliferation, migration, and invasion, and facilitated cell apoptosis by targeting miR-4319 in AML cells. Moreover, as a target of miR-4319, EIF5A2 overexpression overturned the inhibitory effects of miR-4319 upregulation on AML progression. Besides, circ_0058058 sponged miR-4319 to upregulate EIF5A2 expression in AML cells. Conclusion: Circ_0058058 knockdown inhibited cell proliferation, migration, and invasion, but accelerated cell apoptosis by reducing EIF5A2 expression by targeting miR-4319, suggesting that circ_0058058 could be a therapeutic target for the treatment of AML.

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Circ_0058058 基因敲除可通过海绵状 miR-4319 调控 EIF5A2 的表达,从而抑制急性髓性白血病的进展。
背景:急性髓性白血病(AML)是成人中最常见的急性白血病。环状 RNA(circRNA)参与了包括 AML 在内的许多人类癌症的恶化过程。在这项研究中,作者调查了 circ_0058058 在 AML 进展中的作用和潜在机制。研究方法通过实时定量聚合酶链反应测定 circ_0058058、microRNA-4319(miR-4319)和真核启动因子 5A2(EIF5A2)的表达。细胞增殖、凋亡、迁移和侵袭分别通过细胞计数试剂盒-8(CCK-8)、细胞集落形成、流式细胞术和透孔试验进行评估。通过 Western 印迹法检测了相关蛋白质的水平。通过双荧光素酶报告实验验证了 circ_0058058、miR-4319 和 EIF5A2 之间的联系。结果在急性髓细胞性白血病中,Circ_0058058和EIF5A2增强,而miR-4319下降。通过靶向 miR-4319,Circ_0058058 基因敲除可抑制 AML 细胞的增殖、迁移和侵袭,并促进细胞凋亡。此外,作为miR-4319的靶标,EIF5A2的过表达推翻了miR-4319上调对AML进展的抑制作用。此外,circ_0058058还能上调miR-4319在AML细胞中的EIF5A2表达。结论circ_0058058敲除可抑制细胞增殖、迁移和侵袭,但通过靶向miR-4319减少EIF5A2的表达加速细胞凋亡,这表明circ_0058058可能是治疗AML的一个治疗靶点。
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来源期刊
CiteScore
7.80
自引率
2.90%
发文量
87
审稿时长
3 months
期刊介绍: Cancer Biotherapy and Radiopharmaceuticals is the established peer-reviewed journal, with over 25 years of cutting-edge content on innovative therapeutic investigations to ultimately improve cancer management. It is the only journal with the specific focus of cancer biotherapy and is inclusive of monoclonal antibodies, cytokine therapy, cancer gene therapy, cell-based therapies, and other forms of immunotherapies. The Journal includes extensive reporting on advancements in radioimmunotherapy, and the use of radiopharmaceuticals and radiolabeled peptides for the development of new cancer treatments.
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