miR-139 通过调控 RAP1B 抑制人结直肠癌细胞的增殖。
Regulation of RAP1B by miR-139 suppresses human colorectal carcinoma cell proliferation.
机构信息
Department of Clinical Laboratory, No. 3 People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, PR China.
出版信息
Int J Biochem Cell Biol. 2012 Sep;44(9):1465-72. doi: 10.1016/j.biocel.2012.05.015. Epub 2012 May 27.
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, LS174 T, 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.
背景
微小 RNA（miRNAs）在癌症发生中起着重要作用，但它们在主要癌症中的具体作用尚未完全阐明。
方法
使用实时 PCR 检测 miR-139 在结直肠癌及配对正常组织中的表达水平。通过 miR-139 模拟物、抗 miR-139 和 siRNA RAP1B 在结直肠癌细胞系（SW480、SW620、LS174 T 和 HCT116）中评估 miR-139 的潜在功能。
结果
在本研究中，我们确定 miR-139 在结直肠癌（CRC）组织中下调。较低的 miR-139 表达与 CRC 的更晚期和 CRC 患者的总生存率降低相关。在人 CRC 细胞中外源性表达 miR-139 可降低细胞生长和致瘤性，而 miR-139 的沉默则促进了细胞生长。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 沉默则上调了报告基因的表达。RAP1B 的 RNAi 介导的敲低可模拟 miR-139 的抗增殖作用，而 RAP1B 的过表达则可阻断 miR-139 在 CRC 细胞中的抗增殖作用。
结论
综上所述，这些结果表明 miR-139 通过直接靶向 RAP1B 降低增殖，将 miR-139 定义为 CRC 中的一种新的潜在肿瘤抑制 miRNA。
Zotero 插件