Abstract 980: Small molecule inhibitor of miR-155, SMM155I, inhibits epithelial-mesenchymal transition and tumor growth in cancer cells overexpressing miR-155

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Accumulating studies have shown that miR-155 is frequently up-regulated in a various types of human malignancy. Expression of miR-155 induces epithelial-mesenchymal transition (EMT), transformation, tumor growth and metastasis as well as chemoresistance, whereas inhibition of miR-155 reverses these processes. Here we report the discovery of a small molecule miR-155 inhibitor, SMM155I, by screening the National Cancer Institute Diversity Set. SMM155I directly binds to miR-155 and inhibits miR-155 interaction with its targeted mRNAs without effect on expression of miR-155 and other miRs. The inhibition of miR-155 by SMM155I resulted in suppression of cell migration, invasion and EMT in human cancer cells that harbor elevated miR-155. Furthermore, SMM155I potently inhibited tumor growth in nude mice of human cancer cells in which miR-155 is aberrantly expressed but not of those cancer cells in which it is not. These findings provide strong evidence for pharmacologically targeting miR-155 for anticancer drug discovery. Citation Format: Cheng-Xiong Xu, William Kong, Donghwa Kim, Edward Richards, Fei Yan, Yueling Li, Domenico Coppola, Jin Q. Cheng. Small molecule inhibitor of miR-155, SMM155I, inhibits epithelial-mesenchymal transition and tumor growth in cancer cells overexpressing miR-155. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 980. doi:10.1158/1538-7445.AM2014-980