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微小RNA-379-5p通过靶向肝细胞癌中的FAK/AKT信号传导抑制肿瘤侵袭和转移。

MicroRNA-379-5p inhibits tumor invasion and metastasis by targeting FAK/AKT signaling in hepatocellular carcinoma.

作者信息

Chen Jing-Song, Li Hua-Shu, Huang Jiong-Qiang, Dong Shi-Hao, Huang Zhi-Jie, Yi Wei, Zhan Gao-Fang, Feng Ju-Tao, Sun Jian-Cong, Huang Xiao-Hui

机构信息

Department of Gastrointestinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510120, China.

Department of Gynecology and Obstetrics, The Second People's Hospital of Liwan District, Guangzhou 510160, China.

出版信息

Cancer Lett. 2016 May 28;375(1):73-83. doi: 10.1016/j.canlet.2016.02.043. Epub 2016 Mar 2.

Abstract

Some microRNAs (miRNAs) have been implicated in hepatocellular carcinoma (HCC) development and progression. However, the roles and mechanisms of several miRNAs in HCC remain poorly understood. Here, we report that miR-379-5p, which is down-regulated in HCC tissues and cell lines, is associated with advanced TNM stage and metastasis in HCC. The ectopic overexpression of miR-379-5p inhibited HCC cell migration, invasion, epithelial-to-mesenchymal transition (EMT) and metastasis both in vitro and in vivo. Conversely, miR-379 knockdown increased migration, invasion and EMT in HCC cells. Moreover, miR-379-5p exerted this function by directly targeting focal adhesion kinase (FAK) 3'-UTR and repressing FAK expression, thus leading to suppression of AKT signaling. Furthermore, the tumor suppressive effects of miR-379-5p in HCC cells were reversed by activating AKT signaling or restoring FAK expression. In clinical samples of HCC, miR-379-5p negatively correlated with FAK, which was up-regulated in HCC. Taken together, our findings highlight the important role of miR-379-5p in regulating the EMT and metastasis of HCC by targeting FAK/AKT signaling, suggesting that miR-379-5p may represent a novel potential therapeutic target and prognostic marker for HCC.

摘要

一些微小RNA(miRNA)已被证明与肝细胞癌(HCC)的发生和发展有关。然而,几种miRNA在HCC中的作用和机制仍知之甚少。在此,我们报告miR-379-5p在HCC组织和细胞系中表达下调,与HCC的晚期TNM分期和转移相关。miR-379-5p的异位过表达在体外和体内均抑制HCC细胞的迁移、侵袭、上皮-间质转化(EMT)和转移。相反,miR-379敲低增加了HCC细胞的迁移、侵袭和EMT。此外,miR-379-5p通过直接靶向粘着斑激酶(FAK)的3'-UTR并抑制FAK表达来发挥此功能,从而导致AKT信号通路的抑制。此外,激活AKT信号通路或恢复FAK表达可逆转miR-379-5p在HCC细胞中的肿瘤抑制作用。在HCC临床样本中,miR-379-5p与在HCC中上调的FAK呈负相关。综上所述,我们的研究结果突出了miR-379-5p通过靶向FAK/AKT信号通路在调节HCC的EMT和转移中的重要作用,表明miR-379-5p可能代表HCC一种新的潜在治疗靶点和预后标志物。

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