Chen Hong, Sun Jian Guo, Cao Xue-Wu, Ma Xiao-Gan, Xu Jian-Ping, Luo Fu-Kang, Chen Zheng-Tang
Institute of Cancer Research, Xinqiao Hospital, Third Military Medical University, Xinqiao Street No. 2, Shapingba Di, Chongqing 400037, PR China.
Biochem Biophys Res Commun. 2009 Aug 7;385(4):596-600. doi: 10.1016/j.bbrc.2009.05.113. Epub 2009 May 30.
ERBB2 overexpression occurs in numerous types of primary human tumors and alterations in microRNA (miRNA) expression have been associated with tumor suppression or tumorigenesis in human cancer, nevertheless, little is known about natural miRNAs acting on ERBB2. In this study, bioinformatical analysis of the 3'-UTRs of ERBB2 revealed the target elements for miR-548d-3p and miR-559. Moreover, a predicted miRNA/mRNA interaction experimental validation showed that both miR-548d-3p and miR-559 can interact specifically with the 3'-UTR of the ERBB2 mRNA. And miR-548d-3p plus miR-559 transfection showed a cooperative regulation of translationally repressing ERBB2 mRNA rather than by either miR-548d-3p or miR-559 alone. These results not only support the idea that different miRNAs can simultaneously and cooperatively repress a given target mRNA but also preliminarily validate the role of miR-548d-3p and miR-559 in regulating the ERBB2 expression. These data provide molecular basis for the application of miRNAs in ERBB2-targeted therapy.
ERBB2过表达存在于多种原发性人类肿瘤中，且微小RNA（miRNA）表达的改变与人类癌症中的肿瘤抑制或肿瘤发生相关，然而，关于作用于ERBB2的天然miRNA却知之甚少。在本研究中，对ERBB2的3'-非翻译区进行生物信息学分析，揭示了miR-548d-3p和miR-559的靶标元件。此外，一项预测的miRNA/mRNA相互作用实验验证表明，miR-548d-3p和miR-559均能与ERBB2 mRNA的3'-非翻译区特异性相互作用。并且，miR-548d-3p加miR-559转染显示出对ERBB2 mRNA翻译抑制的协同调节作用，而非单独由miR-548d-3p或miR-559起作用。这些结果不仅支持了不同miRNA可同时协同抑制给定靶标mRNA的观点，还初步验证了miR-548d-3p和miR-559在调节ERBB2表达中的作用。这些数据为miRNA在ERBB2靶向治疗中的应用提供了分子基础。
