Metastasis is a major clinical obstacle in the treatment of gastric cancer (GC) and accounts for the majority of cancer-related mortality. MicroRNAs (miRNAs) have been recently emerged as regulators of metastasis through acting on multiple signaling pathways. In this study, we found that miR-7 is significantly down-regulated in high-metastatic GC cell lines and metastatic tissues. Both gain-of-function and loss-of-function studies showed that increased miR-7 expression significantly reduced migration and invasion of GC cells, while decreased miR-7 expression dramatically enhanced cell migration and invasion. In vivo metastasis assays also shown that overexpression of miR-7 remarkably inhibits GC metastasis. Moreover, the IGF1R oncogene, which is often mutated or amplified in human cancers and has been shown to function as an important regulator of cell growth and tumor invasion, was identified as a direct target of miR-7. RNA interference silencing of IGF1R recapitulated the antimetastic function of miR-7, whereas restoration of IGF1R expression attenuated the function of miR-7 in GC cells. Furthermore, we found that suppression of Snail by miR-7 through targeting IGF1R increased E-cadherin expression and partly reversed the epithelial-mesenchymal transition (EMT). Finally, analyses of the miR-7 and IGF1R level in human primary GC with matched lymph node metastasis tissue arrays revealed that miR-7 is inversely related to the increase of IGF1R expression. The present study provides an insight into the specific biological behavior of miR-7 in EMT and tumor metastasis. This novel miR-7/IGF1R/Snail axis would be helpful in the therapeutic application to block GC metastasis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 2304. doi:1538-7445.AM2012-2304