Abstract 3117: Hsa-miR-140-5p inhibits colorectal cancer stem cell invasion and metastasis by suppressing Smad2 and autophagy

Abstract

Abstract Colorectal cancer is one of the most common cancers and frequently metastasizes to the liver. TGF-β signaling has been shown to regulate cancer metastasis by promoting epithelial to mesenchymal transition and cancer stem cell (CSC) phenotypes. Smad2 is a key element downstream of TGF-β. In this study, we showed that hsa-hsa-miR-140-5p-5p directly targets Smad2 and overexpression of hsa-miR-140-5p in colorectal cancer cell lines decreases Smad2 expression level, which leads to decreased level of cell invasion and proliferation, as well as increasing cell cycle arrest. Ectopic expression of hsa-miR-140-5p in colorectal CSCs inhibited CSC growth and sphere formation in vitro by disrupting autophagy, an essential process for cancer cell survival and chemoresistance. We have systematically identified the targets of hsa-miR-140-5p involved in autophagy. Furthermore, overexpression of hsa-miR-140-5p in CSCs abolished the tumor formation as well as metastasis in vivo by using subcutaneous xenografts and tail vein injection of CSCs in NOD/SCID mice. In addition, there is a progressive loss of hsa-miR-140-5p expression from normal colorectal mucosa to primary tumor tissues, with further reduction in liver metastatic tissues, quantified by qRT-PCR. The functional and clinical significance of hsa-miR-140-5p suggests that it is a key regulator in colorectal cancer progression and metastasis. As a result, it may have potential as a novel therapeutic molecule to treat colorectal cancer. Citation Format: Haiyan Zhai, Andrew Fesler, Jingfang Ju. Hsa-miR-140-5p inhibits colorectal cancer stem cell invasion and metastasis by suppressing Smad2 and autophagy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 3117. doi:10.1158/1538-7445.AM2015-3117