Wang Shihua, Bian Chunjing, Yang Zhuo, Bo Ye, Li Jing, Zeng Lifen, Zhou Hong, Zhao Robert Chunhua
Center of Tissue Engineering, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, School of Basic Medicine Peking Union Medical College, Beijing 100005, P.R. China.
Int J Oncol. 2009 May;34(5):1461-6.
MicroRNAs (miRNAs) represent a class of small non-coding RNAs regulating gene expression by inducing RNA degradation or interfering with translation. Aberrant miRNA expression has been described for several human malignancies. Herein, we show that miR-145 is down-regulated in human cancer cell line MCF-7 when compared to normal human mammary epithelial cell line MCF10A. Overexpression of miR-145 by plasmid inhibits MCF-7 cell growth and induces apoptosis. Subsequently, RTKN is identified as a potential miR-145 target by bioinformatics. Using reporter constructs, we show that the RTKN 3' untranslated region (3'UTR) carries the directly binding site of miR-145. Additionally, overexpression of miR-145 in MCF-7 reduces RTKN protein expression as well as mRNA level. Furthermore, down-regulation of RTKN by siRNA can inhibit MCF-7 cell growth. Taken together, we propose that loss of miR-145 may provide a selective growth advantage for MCF-7 by targeting RTKN.
微小RNA（miRNA）是一类小的非编码RNA，通过诱导RNA降解或干扰翻译来调节基因表达。在几种人类恶性肿瘤中都有异常的miRNA表达的描述。在此，我们表明，与正常人乳腺上皮细胞系MCF10A相比，miR-145在人癌细胞系MCF-7中表达下调。通过质粒过表达miR-145可抑制MCF-7细胞生长并诱导细胞凋亡。随后，通过生物信息学鉴定出RTKN是miR-145的潜在靶标。使用报告基因构建体，我们表明RTKN 3'非翻译区（3'UTR）携带miR-145的直接结合位点。此外，MCF-7中miR-145的过表达降低了RTKN蛋白表达以及mRNA水平。此外，通过siRNA下调RTKN可抑制MCF-7细胞生长。综上所述，我们提出miR-145的缺失可能通过靶向RTKN为MCF-7提供选择性生长优势。
