上调hsa-miR-625-5p通过ILK/AKT通路抑制急性髓系白血病细胞的侵袭

Sahar Samieyan Dehkordi, S. Mousavi, Marzieh Ebrahimi, S. Alizadeh, Amir Abbas Hedayati Asl, Monireh Mohammad, Bahareh Aliabedi
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引用次数: 0

摘要

目的急性髓性白血病(Acute myeloid leukemia, AML)以造血干细胞(primary hematopoietic stem cells, hsc)在血液和骨髓中的分化和生长异常为特征。在许多研究中,miR-625-5p已被证明可以抑制下游通路影响整合素连接激酶(ILK)信号通路的转移和侵袭。已经证明,miR-625-5p在AML细胞系中表达降低。本研究旨在探讨miR-625-5p上调对体外KG1细胞系侵袭的影响。材料和方法在本实验研究中,我们通过ILK/AKT通路研究了miR-625-5p上调对KG1细胞系侵袭的影响。采用病毒法转染后,采用侵袭试验评估细胞侵袭,采用定量聚合酶链反应(qPCR)和western blotting检测miR-625-5p基因和蛋白水平。流式细胞术检测CXCR4水平。结果mir -625-5p转染的KG1细胞侵袭性明显降低(P<0.01), ILK、NF-κB、COX2基因表达水平明显低于对照组(P<0.01)。相比之下,转染mir -625-5p的KG1细胞中MMP9、AP1和AKT显著升高(分别为P<0.01、P<0.001和P<0.01), GSK3β无显著变化。NF-κB蛋白水平降低(P<0.01), MMP9蛋白水平升高,但差异不显著。与对照组相比,CXCR4的表达显著降低(P<0.01)。结论miR-625-5p通过ILK途径导致AML细胞系细胞侵袭减少。因此,这可能是未来aml相关研究的一个突破。然而,需要进一步的研究来支持这一论点。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Upregulation of hsa-miR-625-5p Inhibits Invasion of Acute Myeloid Leukemia Cancer Cells through ILK/AKT Pathway
Objective Acute myeloid leukemia (AML) is characterized by abnormalities of differentiation and growth of primary hematopoietic stem cells (HSCs) in the blood and bone marrow. In many studies, miR-625-5p has been shown to inhibit downstream pathways from affecting the metastasis and invasion of the integrin-linked kinase (ILK) signaling pathway. It has been proved that the expression of miR-625-5p decreases in AML cell lines. This study aimed to investigate the effect of miR-625-5p upregulation on the invasion of KG1 ell line in vitro. Materials and Methods In this experimental study, we investigated the impact of upregulation of miR-625-5p on invasion via the ILK/AKT pathway in the KG1 cell line. After transfection using the viral method, the cellular invasion was assessed by invasion assay and the levels of miR-625-5p genes and protein were evaluated by quantitative polymerase chain reaction (qPCR) and western blotting. Moreover, CXCR4 level was assessed by flow cytometry. Results The invasion significantly reduced in MiR-625-5p-transfected KG1 cells (P<0.01) that was concomitant with remarkably decreasing in the expression levels of ILK, NF-κB, and COX2 genes compare with the control group (P<0.01). Incontrast, MMP9, AP1, and AKT significantly increased (P<0.01, P<0.001 and P<0.01, respectively) and GSK3β did not change significantly in MiR-625-5p-transfected KG1 cells. The protein level of NF-κB decreased (P<0.01) and MMP9 increased, however it was not significant. Moreoever, the expression of CXCR4 was significantly lower (P<0.01) in comparison with the control group. Conclusion miR-625-5p leads to a reduction in cell invasion in the AML cell line through ILK pathway. Therefore, it could be a breakthrough in future AML-related research. However, further studies are needed to support this argument.
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