HOXC6-Mediated miR-188-5p Expression Induces Cell Migration through the Inhibition of the Tumor Suppressor FOXN2

Homeobox C6 (HOXC6) is a transcription factor that plays a role in the malignant progression of various cancers. However, the roles of HOXC6 and its regulatory mechanism remain unclear. In this study, we used microRNA (miRNA) regulatory networks to identify key regulatory interactions responsible for HOXC6-mediated cancer progression. In microarray profiling of miRNAs, the levels of miRNAs such as hsa-miR-188-5p, hsa-miR-8063, and hsa-miR-8064 were significantly increased in HOXC6-overexpressing cells. Higher positive expression rates of HOXC6 and miR-188-5p were observed in malignant cancer. We also found that HOXC6 significantly upregulated miR-188-5p expression. The underlying function of HOXC6-mediated miR-188-5p expression was predicted through TargetScan and the MiRNA Database. Overexpression of mir-188-5p inhibited the expression of forkhead box N2 (FOXN2), a tumor suppressor gene. Furthermore, in the luciferase assay, miR-188-5p bound to the 3'-UTR of FOXN2 and was mainly responsible for the dysregulation of FOXN2 expression. Silencing FOXN2 induced cell migration, and the effect of FOXN2 silencing was enhanced when the HOXC6/miR-188-5p axis was induced. These results suggest that HOXC6/miR-188-5p may induce malignant progression in cancer by inhibiting the activation of the FOXN2 signaling pathway.