使用报告文库系统鉴定肿瘤抑制物microRNA-34a的靶标。,Proceedings of the National Academy of Sciences of the United States of America

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使用报告文库系统鉴定肿瘤抑制物microRNA-34a的靶标。
Proceedings of the National Academy of Sciences of the United States of America ( IF 9.4 ) Pub Date : 2017-03-29 , DOI: 10.1073/pnas.1620019114
Yoshiaki Ito ₁ , Atsushi Inoue ₂ , Timothy Seers _{1,

3} , Yukari Hato ₄ , Arisa Igarashi ₂ , Tatsuya Toyama ₄ , Konstantin D Taganov ₅ , Mark P Boldin ₆ , Hiroshi Asahara _{2,

7,

8,

9}

Affiliation

Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo, Tokyo 113-8519, Japan.
Department of Systems BioMedicine, National Research Institute for Child Health and Development, Setagaya, Tokyo 157-8535, Japan.
Imperial College London, South Kensington, London SW7 2AZ, United Kingdom.
Department of Breast Surgery, Nagoya City University Graduate School of Medical Sciences, Nagoya, Aichi 467-8601, Japan.
Division of Biology, California Institute of Technology, Pasadena, CA 91125.
Department of Molecular and Cellular Biology, Beckman Research Institute, City of Hope, Duarte, CA 91010.
Department of Systems BioMedicine, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (TMDU), Bunkyo, Tokyo 113-8519, Japan;
Core Research for Evolutional Science and Technology (CREST), Japan Agency for Medical Research and Development (AMED), Tokyo 100-0004, Japan.
Department of Experimental Medicine, The Scripps Research Institute, San Diego, CA 92131.

miRNA通过靶向特定的mRNA在各种生物学过程中发挥关键作用。目前鉴定miRNA靶标的方法不足以阐明miRNA调控网络。在这里，我们使用荧光素酶报道基因文库创建了一个基于细胞的筛选系统，该文库由4,891个全长cDNA组成，每个cDNA均已整合到荧光素酶基因的3'UTR中。使用此报告文库系统，我们进行了miR-34a（一种肿瘤抑制miRNA）的靶标筛选。我们确定了以前表征和以前未表征的目标。MDA-MB-231乳腺癌细胞中miR-34a过表达抑制了这些先前无法识别的靶标的表达。在这些靶标中，GFRA3对于MDA-MB-231细胞的生长至关重要，其表达与乳腺癌患者的总体生存率相关。此外，发现GFRA3通过miR-34a的编码区直接调控。这些数据表明，该系统可用于阐明miRNA的功能和网络。

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更新日期：2017-04-12

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