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Circ_0058058敲低通过海绵化miR-4319调节表达来抑制急性髓系白血病进展。

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

作者信息

Zhang Ting, Zhou Ying, Guan Jun, Cheng Hui

机构信息

Department of Hematology, Wuhan No.1 Hospital, Wuhan, China.

出版信息

Cancer Biother Radiopharm. 2023 Dec;38(10):738-748. doi: 10.1089/cbr.2020.4170. Epub 2021 Jan 19.

Abstract

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. The expression of circ_0058058, microRNA-4319 (miR-4319), and eukaryotic initiation factor 5A2 () 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 was verified by dual-luciferase reporter assay. Circ_0058058 and 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, overexpression overturned the inhibitory effects of miR-4319 upregulation on AML progression. Besides, circ_0058058 sponged miR-4319 to upregulate expression in AML cells. Circ_0058058 knockdown inhibited cell proliferation, migration, and invasion, but accelerated cell apoptosis by reducing expression by targeting miR-4319, suggesting that circ_0058058 could be a therapeutic target for the treatment of AML.

摘要

急性髓系白血病(AML)是成人中最常见的急性白血病。环状RNA(circRNAs)参与包括AML在内的许多人类癌症的恶化过程。在本研究中,作者探究了circ_0058058在AML进展中的作用及潜在机制。通过定量实时聚合酶链反应测定circ_0058058、微小RNA-4319(miR-4319)和真核起始因子5A2()的表达。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Transwell实验评估细胞增殖、凋亡、迁移和侵袭。通过蛋白质印迹法检测相关蛋白水平。通过双荧光素酶报告基因实验验证circ_0058058、miR-4319和之间的联系。在AML中,circ_0058058和升高,而miR-4319降低。敲低circ_0058058可抑制AML细胞的增殖、迁移和侵袭,并通过靶向miR-4319促进细胞凋亡。此外,作为miR-4319的靶标,过表达可逆转miR-4319上调对AML进展的抑制作用。此外,circ_0058058通过海绵吸附miR-4319上调AML细胞中的表达。敲低circ_0058058可抑制细胞增殖、迁移和侵袭,但通过靶向miR-4319降低表达来加速细胞凋亡,提示circ_0058058可能成为治疗AML的一个治疗靶点。

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