microRNA-219-5p inhibits epithelial-mesenchymal transition and metastasis of colorectal cancer by targeting LEF1

Abstract

Aberrant expression of microRNAs (miRs) has been shown to play a critical role in the pathogenesis and progression of tumors. miR-219-5p has been reported to be abnormally expressed in some types of human tumors. However, the mechanism between miR-219-5p and colorectal cancer (CRC) metastasis remains unclear. In this study, miR-219-5p was found to be downregulated in CRC tissue compared with matched normal tissue. Through luciferase reporter assay, we demonstrated lymphoid enhancer-binding factor 1 (LEF1) as a direct target of miR-219-5p. Over-expression of miR-219-5p could inhibit motility, migration and invasion of CRC cells, and inhibit epithelial-mesenchymal transition (EMT). Furthermore, silencing LEF1 phenocopied this metastasis-suppressive function. The recovery experiment showed that re-expression of LEF1 rescued this suppressive effect on tumor metastasis and reversed the expression of EMT markers caused by miR-219-5p. Additionally, we demonstrated that miR-219-5p exerted this tumor-suppressive function by blocking the activation of the AKT and ERK pathways. Finally, nude mice experiment showed that miR-219-5p reduced the lung metastasis ability of CRC cells. Taken together, our findings indicate that miR-219-5p inhibits metastasis and EMT of CRC by targeting LEF1 and suppressing the AKT and ERK pathways, which may provide a new antitumor strategy to delay CRC metastasis.

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