Insulin growth factor signaling is regulated by microRNA-486, an underexpressed microRNA in lung cancer
Menée sur des échantillons tumoraux prélevés sur 81 patients atteints d'un cancer du poumon non à petites cellules de stade 1, cette étude met en évidence des mécanismes par lesquels le micro-ARN 486, qui régule la signalisation du facteur de croissance analogue à l'insuline, joue un rôle de suppresseur de tumeurs
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.