MiR-542-3p inhibits metastasis and epithelial- mesenchymal transition of hepatocellular carcinoma by targeting UBE3C
MiR-542-3p inhibits metastasis and epithelial- mesenchymal transition of hepatocellular carcinoma by targeting UBE3C
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MiR-542-3p 通过靶向 UBE3C 抑制肝细胞癌的转移和上皮间质转化。
DOI：
10.1016/j.biopha.2017.06.070
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发表时间：
2017-09-01
影响因子：
7.5
通讯作者：
Liu, Qingguang
中科院分区：
文献类型：
--
作者：
Tao, Jie;Liu, Zhikui;Liu, Qingguang
越来越多的证据表明，异常的miRNAs有助于肝细胞癌（HCC）的发生和发展。然而，各种miRNA在HCC中的作用仍有待确定。在目前的研究中，我们证实了miR-542- 3 p在HCC组织和细胞系中的表达降低。我们的临床分析显示，下调的miR-542- 3 p表达与不良预后特征（包括晚期TNM分期和静脉浸润）显著相关。此外，我们证实了miR-542- 3 p是一种新的独立的预测HCC患者5年生存率的预后标志物。miR-542- 3 p的异位过表达抑制了细胞的迁移、侵袭和EMT进程，而下调miR-542- 3 p则逆转了这种作用。此外，miR-542- 3 p可通过直接与UBE 3C的30-UTR结合来调控UBE 3C。在肝癌临床样本中，miR-542- 3 p与UBE 3C呈负相关，UBE 3C在肝癌中上调。UBE 3C表达的改变至少部分地消除了miR-542- 3 p对HCC细胞的迁移、侵袭和EMT进展的影响。结论：miR-542- 3 p作为抑癌基因通过靶向UBE 3C调控HCC的EMT和转移，可能成为HCC治疗的新靶点和预后标志物。(C)2017年Elsevier Masson SAS。All rights reserved.
Accumulating evidence demonstrates that aberrant miRNAs contribute to hepatocellular carcinoma (HCC) development and progression. However, the roles of various miRNAs in HCC remain to be determined. In present research, we confirmed that a reduced miR-542-3p expression was present in HCC tissues and cell lines. Our clinical analysis revealed that the down-regulated miR-542-3p expression was significantly correlated with poor prognostic features including advanced TNM stage and venous infiltration. Moreover, we confirmed that miR-542-3p was a novel independent prognostic marker for predicting 5-year survival of HCC patients. The ectopic overexpression of miR-542-3p inhibited cell migration, invasion and EMT progress, while down-regulated miR-542-3p reversed the effect. In addition, miR-542-3p could regulate UBE3C by directly binding to its 30-UTR. In clinical samples of HCC, miR-542-3p inversely correlated with UBE3C, which was upregulated in HCC. Alternation of UBE3C expression at least partially abolished the migration, invasion and EMT progress effects of miR-542-3p on HCC cells. In conclusion, our results indicated that miR-542-3p functioned as a tumor suppressor gene in regulating the EMT and metastasis of HCC via targeting UBE3C, and may represent a novel potential therapeutic target and prognostic marker for HCC. (C) 2017 Elsevier Masson SAS. All rights reserved.