Esquela-Kerscher Aurora, Trang Phong, Wiggins Jason F, Patrawala Lubna, Cheng Angie, Ford Lance, Weidhaas Joanne B, Brown David, Bader Andreas G, Slack Frank J
Department of Molecular, Cellular and Developmental Biology, Yale University, New Haven, Connecticut 06520, USA.
Cell Cycle. 2008 Mar 15;7(6):759-64. doi: 10.4161/cc.7.6.5834. Epub 2008 Mar 3.
MicroRNAs have been increasingly implicated in human cancer and interest has grown about the potential to use microRNAs to combat cancer. Lung cancer is the most prevalent form of cancer worldwide and lacks effective therapies. Here we have used both in vitro and in vivo approaches to show that the let-7 microRNA directly represses cancer growth in the lung. We find that let-7 inhibits the growth of multiple human lung cancer cell lines in culture, as well as the growth of lung cancer cell xenografts in immunodeficient mice. Using an established orthotopic mouse lung cancer model, we show that intranasal let-7 administration reduces tumor formation in vivo in the lungs of animals expressing a G12D activating mutation for the K-ras oncogene. These findings provide direct evidence that let-7 acts as a tumor suppressor gene in the lung and indicate that this miRNA may be useful as a novel therapeutic agent in lung cancer.
微小RNA越来越多地与人类癌症相关联，并且人们对于使用微小RNA对抗癌症的潜力的兴趣也日益增加。肺癌是全球最常见的癌症形式，且缺乏有效的治疗方法。在此，我们使用了体外和体内方法来表明let-7微小RNA直接抑制肺癌的生长。我们发现let-7在培养中抑制多种人类肺癌细胞系的生长，以及免疫缺陷小鼠体内肺癌细胞异种移植物的生长。使用已建立的原位小鼠肺癌模型，我们表明经鼻给予let-7可减少在表达K-ras癌基因G12D激活突变的动物肺部的体内肿瘤形成。这些发现提供了直接证据，证明let-7在肺部作为肿瘤抑制基因起作用，并表明这种微小RNA可能作为肺癌的新型治疗剂有用。
