MicroRNA-34a suppresses colorectal cancer metastasis by regulating notch signaling

Abstract

Dysregulation of microRNA (miRNA/miR) expression is causally associated with cancer initiation and progression. However, the precise mechanisms by which dysregulated miRNAs induce colorectal tumorigenesis remain unknown. In the present study, downregulation of miR-34a was identified in colorectal cancer cell lines and clinical specimens. Clinical studies revealed that miR-34a expression was negatively associated with distant metastasis, and positively associated with differentiation and survival of human colorectal cancer specimens. In vitro miRNA functional assays demonstrated that miR-34a bound to the putative 3’-untranslated regions of Notch1 and Jagged1 in SW480 cells, and thereby attenuated the migration and invasion of the colon cancer cells. It was additionally identified that miR-34a downregulated the expression of vimentin and fibronectin via Notch1 and Jagged1. Overall, these data indicate that miR-34a serves a key role in suppressing colorectal cancer metastasis by targeting and regulating Notch signaling.