miR-145 inhibits breast cancer cell growth through RTKN
miR-145 inhibits breast cancer cell growth through RTKN
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DOI：
10.3892/ijo_00000275
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发表时间：
2009-05-01
影响因子：
5.2
通讯作者：
Zhao, Robert Chunhua
中科院分区：
文献类型：
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作者：
Wang, Shihua;Bian, Chunjing;Zhao, Robert Chunhua
MicroRNAs(MiRNAs)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的表达。MiRNA的异常表达已经在几种人类恶性肿瘤中被描述。在这里，我们发现miR-145在人类癌细胞株MCF-7中的表达下调，与正常的人乳腺上皮细胞株MCF10A相比。MiR-145过表达可抑制MCF-7细胞生长并诱导细胞凋亡。随后，RTKN被生物信息学确定为潜在的miR-145靶点。利用报告构建法，我们发现RTKN 3‘非翻译区(3’UTR)携带miR-145的直接结合位点。此外，在MCF-7细胞中过表达miR-145会降低RTKN的蛋白表达和mRNA水平。此外，siRNA下调RTKN可以抑制MCF-7细胞的生长。综上所述，我们认为miR-145的缺失可能通过靶向RTKN为MCF-7细胞提供选择性生长优势。
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.