Ftx non coding RNA-derived miR-545 promotes cell proliferation by targeting RIG-I in hepatocellular carcinoma.
Ftx non coding RNA-derived miR-545 promotes cell proliferation by targeting RIG-I in hepatocellular carcinoma.
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Ftx 非编码 RNA 衍生的 miR-545 通过靶向肝细胞癌中的 RIG-I 促进细胞增殖。
DOI：
10.18632/oncotarget.8129
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发表时间：
2016-05-03
期刊：
影响因子：
--
通讯作者：
Liu Q
中科院分区：
文献类型：
--
作者：
Liu Z;Dou C;Yao B;Xu M;Ding L;Wang Y;Jia Y;Li Q;Zhang H;Tu K;Song T;Liu Q
肝细胞癌（HCC）是全球第三大癌症相关死亡原因。越来越多的研究表明，多种lncRNA的异常表达参与了肝癌的发生。本研究选择lncRNA Ftx作为靶基因，研究其对肝癌细胞的作用，并探讨其可能的作用机制。我们证明了lncRNA Ftx和Ftx衍生的miR-545在HCC组织和细胞中均上调。miR-545与lncRNA Ftx表达呈正相关。值得注意的是，临床相关性分析显示，lncRNA Ftx和miR-545的高表达与不良预后特征相关，并降低了HCC患者的5年总生存期（OS）和无病生存期（DFS）。我们发现miR-545是Ftx诱导的HCC细胞生长促进中的关键介质。随后，我们将RIG-I鉴定为miR-545的直接靶点。RIG-I在HCC组织中表达下调，且与miR-545表达呈负相关。我们的数据显示，RIG-I的异位表达消除了lncRNA Ftx或miR-545对HCC细胞的影响。LncRNA Ftx/miR-545介导的RIG-I下调导致体外和体内Akt磷酸化增加。Akt磷酸化的抑制消除了lncRNA Ftx/miR-545对HCC细胞的作用。总之，我们的研究表明，新的途径lncRNA Ftx/miR-545/RIG-I通过激活PI 3 K/Akt信号促进HCC的发展，它可能作为一个新的预后生物标志物和HCC的治疗靶点。
Hepatocellular carcinoma (HCC) is the third cause of cancer-related death worldwide. Accumulating studies have demonstrated that aberrant expression of several lncRNAs was found to be involved in the hepatocarcinogenesis. In this study, a lncRNA Ftx was chosen to investigate its effects on HCC cells, and clarify the possible mechanism. We demonstrated that the lncRNA Ftx and Ftx-derived miR-545 were up-regulated in both HCC tissues and cells. MiR-545 was positively correlated with lncRNA Ftx expression. Notably, clinical association analysis revealed that the high expression of lncRNA Ftx and miR-545 was associated with poor prognostic features, and conferred a reduced 5-year overall survival (OS) and disease-free survival (DFS) of HCC patients. We found that miR-545 was a pivotal mediator in Ftx-induced promotion of HCC cell growth. Subsequently, we identified RIG-I as a direct target of miR-545. The expression of RIG-I was downregulated in HCC tissues and was inversely correlated with miR-545 expression. Our data revealed that ectopic expression of RIG-I abrogated the effects of lncRNA Ftx or miR-545 on HCC cells. LncRNA Ftx/miR-545-mediated downregulation of RIG-I led to increased Akt phosphorylation in vitro and in vivo. Inhibition of Akt phosphorylation abolished the effects of lncRNA Ftx/miR-545 on HCC cells. In conclusion, our study demonstrates that the novel pathway lncRNA Ftx/miR-545/RIG-I promotes HCC development by activating PI3K/Akt signaling, and it may serve as a novel prognostic biomarker and therapeutic target for HCC.
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影响因子：
14.9
作者：
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影响因子：
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作者：
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影响因子：
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作者：
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通讯作者：
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影响因子：
4.8
作者：
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通讯作者：
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DOI：
10.14791/btrt.2014.2.1.1
发表时间：
2014-04
期刊：
Brain tumor research and treatment
影响因子：
--
作者：
Park JY;Lee JE;Park JB;Yoo H;Lee SH;Kim JH
通讯作者：
Kim JH