Novel microRNAs downregulated in breast cancer tumors bind to the 3’UTR of SNAIL, SLUG, ZEB1 and/or TWIST and decrease metastatic behavior in breast cancer cells

Abstract

Metastasis, the leading cause of cancer-associated deaths, is promoted by transcription factors SNAIL, SLUG, ZEB1 and TWIST through the activation of epithelial- mesenchymal transition (EMT). MicroRNAs can suppress EMT, emerging as candidate molecular biomarkers and novel therapeutic targets. Herein, we evaluated microRNAs downregulated in breast cancer tissues expressing EMT transcription factors, to find new potential regulators of EMT. MiR-30a, miR-1271, miR-196a, miR-202, miR-210, miR-22, miR-331 and miR-34b were validated. Seven microRNAs downregulated luciferase activity through EMT transcription factors 3′UTR, and all microRNAs decreased cell migration, invasion and/or proliferation. In MDA-MB-231 cells, miR-196a and miR-22 decreased endogenous ZEB1 levels, and miR-30a endogenous CCR7 levels. These results suggest that microRNAs studied are novel regulators of EMT through the control of SNAIL, SLUG, ZEB1 and TWIST. They also regulate the metastatic behavior of cancer cells, and may control the development of lymph node metastasis through the regulation of CCR7.