MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells
MicroRNA-7 arrests cell cycle in G1 phase by directly targeting CCNE1 in human hepatocellular carcinoma cells
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MicroRNA-7通过直接靶向人肝癌细胞中的CCNE1使细胞周期停滞在G1期
DOI：
10.1016/j.bbrc.2013.12.095
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发表时间：
2014-01-17
影响因子：
3.1
通讯作者：
Zhang, Rui
中科院分区：
文献类型：
--
作者：
Zhang, Xiao;Hu, Shijie;Zhang, Rui
越来越多的证据表明，miRNA的异常表达是恶性肿瘤的标志，表明miRNA在肿瘤的发生、发展中起着重要作用。miR-7被认为是多种类型癌症中的肿瘤抑制miRNA。然而，miR-7在人类肝细胞癌（HCC）中的作用及其潜在机制仍然是难以捉摸的。在这项研究中，我们发现miR-7的过表达在HCC中将细胞周期阻滞在G1向S转变。结合生物信息学预测、报告基因分析、实时定量PCR（qRT-PCR）和Western blot等方法，证实了G1/S转换的重要介导因子CCNE 1是miR-7的新的直接靶基因之一。进一步的研究表明，CCNE 1的沉默重现了miR-7过表达的作用，而CCNE 1的强制表达逆转了miR-7在细胞周期调控中的抑制作用。最后，qRT-PCR分析显示miR-7和CCNE 1在临床癌组织和多种类型的肿瘤细胞系中存在相互关系。这些发现表明miR-7通过抑制癌基因CCNE 1的表达在肝癌发生中发挥肿瘤抑制作用，并提示miR-7在HCC中的治疗应用。皇冠版权所有（C）2013由Elsevier Inc.发布。All rights reserved.
Growing evidence has demonstrated that the aberrant expression of miRNA is a hallmark of malignancies, indicating the important roles of miRNA in the development and progression of cancer. MiR-7 is considered as a tumor suppressor miRNA in multiple types of cancer. However, the role of miR-7 in human hepatocellular carcinoma (HCC) and its underlying mechanism remain elusive. In this study, we found that overexpression of miR-7 arrested cell cycle at G1 to S transition in HCC. By combinational use of bioinformatic prediction, reporter assay, quantitative real-time PCR (qRT-PCR) and Western blot, we confirmed that CCNE1, an important mediator in G1/S transition is one of new direct target genes of miR-7. Further studies revealed that silencing of CCNE1 recapitulated the effects of miR-7 overexpression, whereas enforced expression of CCNE1 reversed the suppressive effects of miR-7 in cell cycle regulation. Finally, analysis of qRT-PCR showed a reciprocal relationship between miR-7 and CCNE1 in clinical cancer tissues and multiple types of tumor cell lines. These findings indicate that miR-7 exerts tumor-suppressive effects in hepatocarcinogenesis through the suppression of oncogene CCNE1 expression and suggest a therapeutic application of miR-7 in HCC. Crown Copyright (C) 2013 Published by Elsevier Inc. All rights reserved.