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微小RNA-9通过靶向CXC趋化因子受体4在急性髓系白血病中发挥肿瘤抑制作用。

MiR-9 functions as a tumor suppressor in acute myeloid leukemia by targeting CX chemokine receptor 4.

作者信息

Zhu Bingke, Xi Xiaoping, Liu Qiongqiong, Cheng Yingying, Yang Haiping

机构信息

Department of Hematology, The First Affiliated Hospital, College of Clinical Medicine of Henan University of Science and Technology Luoyang 471023, Henan, China.

出版信息

Am J Transl Res. 2019 Jun 15;11(6):3384-3397. eCollection 2019.

Abstract

MicroRNAs (miRNAs) play key roles in the pathogenesis of many cancers, including acute myeloid leukemia (AML). Although miRNA-9 (miR-9) is involved in the leukemogenesis of AML, the underlying mechanisms remain to be elucidated. In this study, we found that miR-9 and C-X-C chemokine receptor 4 (CXCR4) were differentially expressed in myeloid leukemia, particularly in AML. The inverse correlation between miR-9 and CXCR4 was identified in AML samples and cell lines. The AML patients simultaneously with high levels of CXCR4 and low expression of miR-9 possessed poor prognosis. In vitro, miR-9 inhibited the proliferation, apoptosis resistance, migration, and invasion of AML cells. Dual luciferase assays verified CXCR4 as a direct target of miR-9. The suppressive effects of miR-9 on AML cells were counteracted or mimicked by CXCR4 overexpression or depletion, respectively. Overall, this study reveals that miR-9 retards the aggressive behaviors of AML cells by repressing CXCR4. Thus, miR-9/CXCR4 axis may represent a potential therapeutic target for AML.

摘要

微小RNA(miRNA)在包括急性髓系白血病(AML)在内的多种癌症发病机制中发挥关键作用。尽管miRNA - 9(miR - 9)参与AML的白血病发生过程,但其潜在机制仍有待阐明。在本研究中,我们发现miR - 9和C - X - C趋化因子受体4(CXCR4)在髓系白血病中存在差异表达,尤其是在AML中。在AML样本和细胞系中鉴定出miR - 9与CXCR4呈负相关。同时具有高水平CXCR4和低表达miR - 9的AML患者预后较差。在体外,miR - 9抑制AML细胞的增殖、抗凋亡、迁移和侵袭。双荧光素酶测定证实CXCR4是miR - 9的直接靶点。miR - 9对AML细胞的抑制作用分别被CXCR4过表达或缺失所抵消或模拟。总体而言,本研究表明miR - 9通过抑制CXCR4来延缓AML细胞的侵袭行为。因此,miR - 9/CXCR4轴可能是AML的一个潜在治疗靶点。

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