miR-137 is frequently down-regulated in glioblastoma and is a negative regulator of Cox-2
miR-137 is frequently down-regulated in glioblastoma and is a negative regulator of Cox-2
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DOI：
10.1016/j.ejca.2012.02.007
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发表时间：
2012-11-01
影响因子：
8.4
通讯作者：
Jiang, Chuanlu
中科院分区：
文献类型：
--
作者：
Chen, Lingchao;Wang, Xiaofeng;Jiang, Chuanlu
MicroRNAs与癌症密切相关，但其在主要癌症中的具体作用和功能尚未完全阐明。在这项研究中，我们定义了miR-137的表达和功能，我们发现它在胶质瘤样本和胶质瘤细胞中通过qRT-PCR下调。MiR-137在胶质瘤细胞系中的异位表达抑制了细胞的增殖和侵袭。通过计算和表达分析，COX-2被确定为miR-137的候选靶点。在荧光素酶基因下游克隆了30个非编码区的COX-2的报告基因，发现在miR-137存在的情况下，荧光素酶活性降低，这为miR-137是COX-2的直接调节因子提供了有力的证据。表达分析进一步表明，COX-2在胶质瘤中升高，并与患者的生存有关。此外，我们还观察到COX-2基因敲除在胶质瘤细胞中的作用与miR-137基因的作用相似。综上所述，我们的研究表明miR-137的失控在胶质瘤中很常见，其功能的恢复抑制了细胞的增殖和侵袭，提示miR-137可能是一种肿瘤抑制因子。(C)2012爱思唯尔有限公司。保留所有权利。
MicroRNAs are strongly implicated in cancer but their specific roles and functions in the major cancers have yet to be fully elucidated. In this study, we defined the expression and function of miR-137, which we found to be downregulated in glioma samples and glioma cells by qRT-PCR. Ectopic expression of miR-137 in glioma cell lines inhibited proliferation and invasion. Using computational and expression analysis, Cox-2 was identified as a candidate target of miR-137. Reporter assay with 30UTR of Cox-2 cloned downstream of the luciferase gene showed reduced luciferase activity in the presence of miR-137, providing strong evidence that miR-137 was a direct regulator of Cox-2. Expression analysis further revealed that Cox-2 was elevated in glioma and associated with survival of patients. Furthermore, we observed that Cox-2 knockdown resulted in effects similar to those with miR-137 transfection in glioma cells. In conclusion, our study demonstrates that miR-137 deregulation is common in glioma, and restoration of its function inhibits cell proliferation and invasion, suggesting that miR-137 may act as a tumour suppressor. (C) 2012 Elsevier Ltd. All rights reserved.