MicroRNA-191 promotes hepatocellular carcinoma cell proliferation by has_circ_0000204/miR-191/KLF6 axis
MicroRNA-191 promotes hepatocellular carcinoma cell proliferation by has_circ_0000204/miR-191/KLF6 axis
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DOI：
10.1111/cpr.12635
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发表时间：
2019-07-23
影响因子：
8.5
通讯作者：
Zhu, Xuejun
中科院分区：
文献类型：
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作者：
Tian, Fang;Yu, Chengtao;Zhu, Xuejun
目的MicroRNA是肝细胞癌（HCC）发生发展的重要调控因子。已有研究表明，微小RNA-191（miR-191）在肝细胞癌中发挥重要作用，但其调控机制尚不清楚。在这项研究中，我们研究了miR-191在HCC中的作用，并研究了其潜在的作用机制。材料与方法采用实时荧光定量PCR（qRT-PCR）检测肝癌组织中miR-191的表达。通过使用体外和体内测定来检查miR-191在HCC细胞中的作用。通过qRT-PCR和Western印迹分析确定miR-191的下游靶标。进行双荧光素酶测定以验证miR-191与其靶标之间的相互作用。结果肝癌患者中miR-191的表达明显升高，miR-191表达越高，预后越差。对癌症基因组图谱数据集的分析表明，miR-191与细胞周期进程呈正相关。功能获得和丧失分析显示miR-191促进细胞周期进展和增殖。荧光素酶报告基因检测显示miR-191直接靶向KLF 6 mRNA的3 '非翻译区。此外，环状RNA has_circ_0000204可以与miR-191海绵化，导致miR-191失活。结论本研究揭示了miR-191在肝癌中的作用机制，为肿瘤治疗提供了新的思路。
Objectives MicroRNAs are powerful regulators in hepatocellular carcinoma (HCC) tumorigenesis. MicoRNA-191 (miR-191) has been reported to play an important role in HCC, However, the regulatory mechanism is still unclear. In this study, we investigated the role of miR-191 in HCC and studied its underlying mechanisms of action. Materials and methods The expression of miR-191 in HCC tissues was determined by quantitative real-time PCR (qRT-PCR). The role of miR-191 in HCC cells was examined by using both in vitro and in vivo assays. Downstream targets of miR-191 were determined by qRT-PCR and Western blot analysis. Dual-luciferase assays were performed to validate the interaction between miR-191 and its targets. Results The expression of miR-191 was significantly higher in HCC patients and a higher miR-191 expression predicted poorer prognosis. Analysis of The Cancer Genome Atlas data sets suggested that miR-191 positively correlated with cell cycle progression. Gain and loss of function assays showed that miR-191 promoted cell cycle progression and proliferation. Luciferase reporter assay showed that miR-191 directly targeted the 3'-untranslated region of KLF6 mRNA. Furthermore, circular RNA has_circ_0000204 could sponge with miR-191, resulting in inactivation of miR-191. Conclusions Our study sheds light on the novel underlying mechanism of miR-191 in HCC, which may accelerate the development of cancer therapy.