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MicroRNA-33b 通过靶向 Fli-1 调控的 Notch1 通路调节肝癌细胞的增殖、凋亡和迁移。

MicroRNA-33b regulates hepatocellular carcinoma cell proliferation, apoptosis, and mobility via targeting Fli-1-mediated Notch1 pathway.

机构信息

Department of General Surgery, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

Department of Pathology, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, China.

出版信息

J Cell Physiol. 2020 Oct;235(10):7635-7644. doi: 10.1002/jcp.29673. Epub 2020 Apr 2.

Abstract

MicroRNAs (miRNAs) have been confirmed to play pivotal roles in hepatocellular carcinoma (HCC) carcinogenesis. However, the underlying function of microRNA-33b (miR-33b) in HCC remains unclear. Here, we found that miR-33b level was significantly reduced in both HCC tissues and tumor cell lines. Further, luciferase reporter assay and western blot analysis confirmed that Friend leukemia virus integration 1 (Fli-1) was a direct target of miR-33b. Overexpression of miR-33b dramatically suppressed HCC tumor cell proliferation and cell mobility, but facilitated tumor cell apoptosis in vitro. Besides, restoration of Fli-1 partially attenuated miR-33b-mediated inhibition of cell growth and metastasis via activating Notch1 signaling and its downstream effectors. Our findings demonstrate the important role of miR-33b/Fli-1 axis in HCC progression and provide novel therapeutic candidates for HCC clinical treatment.

摘要

微小 RNA(miRNAs)已被证实在肝细胞癌(HCC)发生发展中发挥关键作用。然而,miR-33b 在 HCC 中的潜在功能仍不清楚。在这里,我们发现 miR-33b 的水平在 HCC 组织和肿瘤细胞系中均显著降低。进一步的荧光素酶报告基因检测和 Western blot 分析证实,Friend 白血病病毒整合 1(Fli-1)是 miR-33b 的直接靶标。miR-33b 的过表达显著抑制 HCC 肿瘤细胞的增殖和迁移,但促进体外肿瘤细胞凋亡。此外,Fli-1 的恢复部分通过激活 Notch1 信号及其下游效应物来减弱 miR-33b 介导的细胞生长和转移抑制作用。我们的研究结果表明 miR-33b/Fli-1 轴在 HCC 进展中的重要作用,并为 HCC 的临床治疗提供了新的治疗靶点。

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