Department of Molecular Virology, Immunology, and Medical Genetics and Division of Hematology, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210.
Proc Natl Acad Sci U S A. 2013 Sep 10;110(37):15043-8. doi: 10.1073/pnas.1307107110. Epub 2013 Aug 26.
MicroRNAs (miRNAs) are small 19- to 24-nt noncoding RNAs that have the capacity to regulate fundamental biological processes essential for cancer initiation and progression. In cancer, miRNAs may function as oncogenes or tumor suppressors. Here, we conducted global profiling for miRNAs in a cohort of stage 1 nonsmall cell lung cancers (n = 81) and determined that miR-486 was the most down-regulated miRNA in tumors compared with adjacent uninvolved lung tissues, suggesting that miR-486 loss may be important in lung cancer development. We report that miR-486 directly targets components of insulin growth factor (IGF) signaling including insulin-like growth factor 1 (IGF1), IGF1 receptor (IGF1R), and phosphoinositide-3-kinase, regulatory subunit 1 (alpha) (PIK3R1, or p85a) and functions as a potent tumor suppressor of lung cancer both in vitro and in vivo. Our findings support the role for miR-486 loss in lung cancer and suggest a potential biological link to p53.
MicroRNAs (miRNAs) 是 19 到 24 个核苷酸的小非编码 RNA，具有调节癌症起始和进展所必需的基本生物过程的能力。在癌症中，miRNAs 可以作为癌基因或肿瘤抑制因子发挥作用。在这里，我们对 81 例 1 期非小细胞肺癌患者的 miRNA 进行了全面分析，并确定与相邻未受累肺组织相比，miR-486 在肿瘤中下调最为明显，提示 miR-486 的缺失可能在肺癌发生中很重要。我们报告说，miR-486 直接靶向胰岛素生长因子 (IGF) 信号通路的成分，包括胰岛素样生长因子 1 (IGF1)、IGF1 受体 (IGF1R) 和磷脂酰肌醇-3-激酶调节亚基 1 (alpha) (PIK3R1，或 p85a)，并在体外和体内均作为肺癌的有效肿瘤抑制因子发挥作用。我们的研究结果支持 miR-486 缺失在肺癌中的作用，并提示与 p53 之间存在潜在的生物学联系。
