MicroRNA-519a promotes tumor growth by targeting PTEN/PI3K/AKT signaling in hepatocellular carcinoma.
MicroRNA-519a promotes tumor growth by targeting PTEN/PI3K/AKT signaling in hepatocellular carcinoma.
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MicroRNA-519a 通过靶向肝细胞癌中的 PTEN/PI3K/AKT 信号传导促进肿瘤生长。
DOI：
10.3892/ijo.2015.3309
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发表时间：
2016-03
影响因子：
5.2
通讯作者：
Yang W
中科院分区：
文献类型：
--
作者：
Tu K;Liu Z;Yao B;Han S;Yang W
MicroRNAs（miRNAs）在肝细胞癌（HCC）的发病机制中起着重要作用。先前的miRNA阵列数据显示，与邻近的非肿瘤组织相比，miR-519 a在HCC组织中上调。然而，miR-519 a在HCC中的功能性作用仍然未被探索。在这项研究中，我们证明了miR-519 a在HCC组织和细胞系中的表达均升高。临床相关性分析显示，miR-519 a高表达与肿瘤体积大、Edmondson-Steiner分级高、TNM分期高、静脉浸润等不良临床病理特征相关。此外，miR-519 a的高表达降低了HCC患者的5年总生存率和无病生存率。此外，我们发现miR-519 a过表达促进了体外HCC细胞增殖和细胞周期进程，但miR-519 a沉默降低了细胞增殖和细胞周期进程。值得注意的是，我们鉴定了磷酸酶和张力蛋白同源物（PTEN）作为HCC细胞中miR-519 a的直接下游靶点和功能性介导物。从机制上讲，PTEN下游的磷脂酰肌醇-3-OH激酶（PI 3 K）/AKT通路对于miR-519 a在HCC细胞中的功能作用是必不可少的。综上所述，我们的研究结果表明miR-519 a通过靶向PTEN介导的PI 3 K/AKT通路促进HCC的肿瘤生长，并可能成为HCC的新的预后生物标志物和治疗靶点。
MicroRNAs (miRNAs) have been found to play fundamental roles in the pathogenesis of hepatocellular carcinoma (HCC). Previous miRNA array data showed that miR-519a was upregulated in HCC tissues compared to adjacent non-tumor tissues. However, the functional role of miR-519a in HCC remains unexplored. In this study, we demonstrated that the expression of miR-519a was elevated in both HCC tissues and cell lines. Clinical association analysis revealed that high expression of miR-519a was correlated with adverse clinicopathological characteristics including large tumor size, high Edmondson-Steiner grading, advanced tumor-node-metastasis (TNM) tumor stage and venous infiltration. Furthermore, high expression of miR-519a conferred a reduced 5-year overall survival and disease-free survival of HCC patients. Moreover, we disclosed that miR-519a overexpression promoted, but miR-519a silencing reduced, HCC cell proliferation and cell cycle progression in vitro. Notably, we identified phosphatase and tensin homolog (PTEN) as a direct downstream target and functional mediator of miR-519a in HCC cells. Mechanistically, phosphatidylinositol-3-OH kinase (PI3K)/AKT pathway, downstream of PTEN, is essential for the functional roles of miR-519a in HCC cells. In conclusion, our results indicate that miR-519a promotes tumor growth of HCC by targeting PTEN-mediated PI3K/AKT pathway, and potentially serves as a novel prognostic biomarker and therapeutic target for HCC.