Regulation of RAP1B by miR-139 suppresses human colorectal carcinoma cell proliferation
Regulation of RAP1B by miR-139 suppresses human colorectal carcinoma cell proliferation
复制标题
miR-139对RAP1B的调节抑制人结直肠癌细胞增殖
DOI：
10.1016/j.biocel.2012.05.015
复制
发表时间：
2012-09-01
影响因子：
4
通讯作者：
Zhang, Jianjun
中科院分区：
文献类型：
--
作者：
Guo, Haiyan;Hu, Xiaobo;Zhang, Jianjun
背景：microRNAs(MiRNAs)与肿瘤发生密切相关，但其在主要肿瘤中的具体作用尚未完全阐明。方法：采用实时荧光定量聚合酶链式反应技术检测miR-139在结直肠癌及其配对正常组织中的表达。利用miR-139模拟物、miR-139抗体和siRNA RAP1B对miR-139在结直肠癌细胞系SW480、SW620、LS174T和HCT116中的潜在功能进行了研究。结果：在本研究中，我们确定miR-139在结直肠癌组织中表达下调。MiR-139的低表达与更晚期的结直肠癌和更低的总存活率相关。MiR-139在人结直肠癌细胞中的异位表达降低了细胞的生长和致瘤性，而沉默miR-139则促进了细胞的生长。机制研究表明，miR-139抑制了与RAP1B 3‘-非翻译区融合的报告基因的活性，而miR-139沉默上调了报告基因的表达。RNAi介导的RAP1B基因敲除抑制了miR-139的抗增殖作用，而RAP1B的过表达则阻断了miR-139介导的抗增殖作用。结论：这些结果表明miR-139通过直接靶向RAP1B来抑制细胞的增殖，从而确定miR-139是一种新的肿瘤抑制基因。(C)2012爱思唯尔有限公司。保留所有权利。
Background: MicroRNAs (miRNAs) are strongly implicated in carcinogenesis, but their specific roles in the major cancers have yet to be fully elucidated.Methods: The expression levels of miR-139 in colorectal carcinoma and paired normal tissues were examined using real-time PCR assays. Potential functions of miR-139 were evaluated in colorectal carcinoma cell lines (SW480, SW620, LS174T, and HCT116) using miR-139 mimics, anti-miR-139, and siRNA RAP1B.Results: In this study, we determined that miR-139 is down-regulated in colorectal carcinoma (CRC) tissues. Lower miR-139 expression correlates with more advanced CRC and lower overall survival of patients with CRC. The ectopic expression of miR-139 in human CRC cells decreased cell growth and tumorigenicity, whereas the silencing of miR-139 promoted cell growth. Mechanistic studies revealed that miR-139 repressed the activity of a reporter gene fused to the 3'-untranslated region of RAP1B, whereas miR-139 silencing up-regulated the expression of the reporter gene. RNAi-mediated knockdown of RAP1B phenocopied the antiproliferative effect of miR-139, whereas the overexpression of RAP1B blocked miR-139-mediated antiproliferative effects in CRC cells.Conclusions: Taken together, these results demonstrated that miR-139 decreases proliferation by directly targeting RAP1B, defining miR-139 as a new putative tumour suppressor miRNA in CRC. (C) 2012 Elsevier Ltd. All rights reserved.