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miR-370-3p 通过抑制 PDLIM1/Wnt/β-catenin 信号通路抑制细胞增殖并诱导慢性髓系白血病细胞凋亡。

MicroRNA-370-3p inhibits cell proliferation and induces chronic myelogenous leukaemia cell apoptosis by suppressing PDLIM1/Wnt/β-catenin signaling.

机构信息

Department of Clinical Laboratory, Zhuji People's Hospital of Zhejiang Province, Shaoxing, China.

出版信息

Neoplasma. 2020 May;67(3):509-518. doi: 10.4149/neo_2020_190612N506. Epub 2020 Jan 27.

DOI:10.4149/neo_2020_190612N506
PMID:31986893
Abstract

Growing evidence has suggested that microRNA-370-3p (miR-370-3p) is downregulated and acts as a suppressor in several cancers. However, the role of miR-370-3p in chronic myeloid leukemia (CML) remains unknown. Here, the expression level and molecular mechanism of miR-370-3p in CML were investigated. Firstly, the expression of miR-370-3p has markedly decreased in the peripheral blood mononuclear cells (PBMCs) of patients with CML and in cell lines. Moreover, miR-370-3p in CML cells upregulated and downregulated proliferation and apoptosis, respectively. Notably, miR-370-3p directly targeted the 3'-untranslated region of PDZ and LIM domain protein 1 (PDLIM1). A negative correlation was observed between the levels of miR-370-3p and PDLIM1 in the PBMCs of patients with CML and healthy volunteers. PDLIM1 was shown to have an oncogenic role in CML cells by promoting proliferation and suppressing apoptosis. Finally, the miR-370-3p-PDLIM1-Wnt/β-catenin signaling axis was indicated to play an important role in CML progression.

摘要

越来越多的证据表明,微小 RNA-370-3p(miR-370-3p)在几种癌症中下调并作为抑制物发挥作用。然而,miR-370-3p 在慢性髓性白血病(CML)中的作用尚不清楚。在这里,研究了 miR-370-3p 在 CML 中的表达水平和分子机制。首先,CML 患者的外周血单个核细胞(PBMCs)和细胞系中 miR-370-3p 的表达明显降低。此外,CML 细胞中的 miR-370-3p 分别上调和下调增殖和凋亡。值得注意的是,miR-370-3p 可直接靶向 PDZ 和 LIM 结构域蛋白 1(PDLIM1)的 3'-非翻译区。CML 患者和健康志愿者 PBMCs 中 miR-370-3p 和 PDLIM1 的水平呈负相关。PDLIM1 通过促进增殖和抑制凋亡在 CML 细胞中发挥致癌作用。最后,表明 miR-370-3p-PDLIM1-Wnt/β-catenin 信号通路在 CML 进展中起重要作用。

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