miR-34a inhibits esophageal squamous cell carcinoma progression via regulation of FOXM1.

Abstract

Downregulation of microRNA-34a (miR-34a) has frequently been observed in esophageal squamous cell carcinoma (ESCC). However, the underlying role and molecular mechanism of miR-34a in ESCC remains largely unknown. In the current study, it was demonstrated that miR-34a was downregulated and forkhead box M1 (FOXM1), a target gene of miR-34a, was upregulated in ESCC tumor tissues. Overexpression of miR-34a decreased FOXM1 mRNA and protein expression in the ESCC cell lines tested (TE-1 and TE-8). Inhibition of miR-34a increased FOXM1 mRNA and protein levels in human esophageal epithelial cells (HEEC). In addition, miR-34a mimics reduced the relative luciferase activity of ESCC cells transfected with FOXM1 3 UTR-WT, but not FOXM1 3 UTR-Mut. The CCK8 assay and scratch wound healing assay showed that overexpression of miR-34a induced inhibition of cell proliferation and cell migration. Additionally, transfection with miR-34a mimics reduced the expression of key genes involved in cell migration (MMP2 and MMP9) in ESCC cells. Thus, the present data demonstrated that miR-34a suppressed ESCC progression by directly targeting FOXM1.