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