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miR-595 通过抑制 NF-κB 信号通路抑制肝癌细胞增殖和转移。

miR-595 suppresses cell proliferation and metastasis in hepatocellular carcinoma by inhibiting NF-κB signalling pathway.

机构信息

Tianjin Key Laboratory of Organic Solar Cells and Photochemical Conversion, Tianjin Key Laboratory of Drug Targeting and Bioimaging, School of Chemistry and Chemical Engineering, Tianjin University of Technology, Tianjin 300384, People's Republic of China.

Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Tianjin Medical University, Tianjin, China.

出版信息

Pathol Res Pract. 2020 Apr;216(4):152899. doi: 10.1016/j.prp.2020.152899. Epub 2020 Feb 17.

Abstract

MicroRNAs (miRNAs) have been proven to be critical regulators of cancer development. To date, many of them are still in urgent need of characterisation, and role of miR-595 in hepatocellular carcinoma (HCC) remains unknown. To better understand the mechanism of miR-595 in HCC development, a series of experiments were carried out to explore the effects of miR-595 on malignant behaviour in HCC. First, we found that miR-595 was downregulated in HCC tissues and cells and tightly associated with poor overall survival in HCC patients. Then, we further demonstrated that miR-595 inhibited cell proliferation, migration and invasion in vitro. Additionally, animal experimental results demonstrated that miR-595 inhibited HCC carcinogenesis in vivo. Moreover, we demonstrated that upregulation of miR-595 expression inhibited the NF-κB signalling pathway in HCC cells. To further uncover the molecular mechanism of miR-595 action on the NF-κB signalling pathway, we identified ABCB1 as a direct target of miR-595 through bioinformatics prediction and supported our results with luciferase assays. Finally, we showed that miR-595 inhibited the NF-κB pathway by suppressing ABCB1 expression in HCC cells. Taken together, our findings uncover a pivotal role for the miR-595/ABCB1/NF-κB axis in HCC development, and this novel axis may be a suitable target for diagnostic or therapeutic interventions in HCC.

摘要

MicroRNAs (miRNAs) 已被证明是癌症发展的关键调控因子。迄今为止,其中许多 miRNA 仍亟待研究,miR-595 在肝细胞癌 (HCC) 中的作用仍不清楚。为了更好地理解 miR-595 在 HCC 发展中的机制,我们进行了一系列实验来探索 miR-595 对 HCC 恶性行为的影响。首先,我们发现 miR-595 在 HCC 组织和细胞中下调,与 HCC 患者的总体生存率密切相关。然后,我们进一步证明 miR-595 抑制 HCC 细胞的体外增殖、迁移和侵袭。此外,动物实验结果表明 miR-595 在体内抑制 HCC 发生。此外,我们证明上调 miR-595 表达抑制 HCC 细胞中的 NF-κB 信号通路。为了进一步揭示 miR-595 对 NF-κB 信号通路作用的分子机制,我们通过生物信息学预测鉴定出 ABCB1 是 miR-595 的直接靶标,并通过荧光素酶实验支持了我们的结果。最后,我们表明 miR-595 通过抑制 HCC 细胞中 ABCB1 的表达来抑制 NF-κB 通路。总之,我们的研究结果揭示了 miR-595/ABCB1/NF-κB 轴在 HCC 发展中的关键作用,该新轴可能是 HCC 诊断或治疗干预的合适靶点。

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