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微小RNA-21通过靶向Krüppel样因子5促进急性髓系白血病的增殖。

MicroRNA-21 promotes proliferation in acute myeloid leukemia by targeting Krüppel-like factor 5.

作者信息

Li Chan, Yan Hua, Yin Jie, Ma Jian, Liao Ang, Yang Shengyou, Wang Lijuan, Huang Yongxiang, Lin Chon, Dong Zhiqiang, Yang Bo, Cao Ting, Liu Guo, Wang Lv

机构信息

Department of Hematology and Oncology, Changzhi Medical College Affiliated Heji Hospital, Changzhi, Shanxi 046000, P.R. China.

Department of Nuclear Medicine, Guizhou Provincial People's Hospital, Guiyang, Guizhou 550000, P.R. China.

出版信息

Oncol Lett. 2019 Sep;18(3):3367-3372. doi: 10.3892/ol.2019.10667. Epub 2019 Jul 25.

Abstract

Abnormal expression of microRNA (miR)-21 has been reported in various types of cancers. However, the role and mechanism of miR-21 remain to be elucidated in acute myeloid leukemia (AML). In the present study, it was observed that miR-21 was upregulated and Krüppel-like factor 5 (KLF5) was downregulated in AML cells compared with normal bone marrow cells. Dual luciferase reporter assays revealed that KLF5 was a direct target of miR-21. Indeed, miR-21 overexpression resulted in a downregulation of KLF5 expression, while miR-21 inhibition had the opposite effect in AML cells. In addition, miR-21 overexpression promoted the proliferation of AML cells . Notably, using a mouse xenograft model, miR-21 overexpression was demonstrated to result in enhanced tumor growth and suppressed KLF5 expression in the xenograft tumors . In conclusion, the present results indicated that miR-21 promoted proliferation through directly regulating KLF5 expression in AML cells. miR-21 may thus serve as an oncogene in AML, providing a potential target for AML therapy.

摘要

据报道,微小RNA(miR)-21在多种癌症中存在异常表达。然而,miR-21在急性髓系白血病(AML)中的作用和机制仍有待阐明。在本研究中,观察到与正常骨髓细胞相比,AML细胞中miR-21上调,而Krüppel样因子5(KLF5)下调。双荧光素酶报告基因检测显示KLF5是miR-21的直接靶标。事实上,miR-21过表达导致AML细胞中KLF5表达下调,而抑制miR-21则产生相反的效果。此外,miR-21过表达促进了AML细胞的增殖。值得注意的是,使用小鼠异种移植模型,证实miR-21过表达导致异种移植肿瘤中肿瘤生长增强且KLF5表达受到抑制。总之,目前的结果表明,miR-21通过直接调节AML细胞中KLF5的表达促进增殖。因此,miR-21可能作为AML中的一种癌基因,为AML治疗提供潜在靶点。

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