HOXC6 유도 miR‐188‐5p에 의한 종양 억제 유전자 FOXN2 조절 기전

Abstract

Homeobox C6 (HOXC6) is a transcription factor that plays a part in malignant progression of various cancers. However, the roles of HOXC6 and its regulatory mechanism remains unclear. In this study, we identified key regulatory interactions responsible for HOXC6 mediated-cancer progression by miRNA regulatory networks. In microarray profiling of miRNA, miRNAs, such as hsa-miR-188-5p, hsa-miR-8063, and hsa-miR-8064 were significantly increased in HOXC6 overexpressed cells. Higher positive expression rate of HOXC6 and mir-188-5p was observed in malignant cancer. We also found that HOXC6 significantly up-regulated mir-188-5p expression. The underlying function of HOXC6 mediated mir-188-5p was predicted through TargetsScan and MiRNA Database. The overexpressing mir-188-5p downregulates the expression of FOXN2, a tumor suppressor gene. Furthermore, in luciferase assay, mir-188-5p bind to the 3’-UTR of FOXN2 and is mainly responsible for the dysregulation of FOXN2. Silencing FOXN2 induced cell migration and the effect of FOXN2 silencing was enhanced when the HOXC6/mir-188-5p signaling pathway was increased. These results suggest that HOXC6/mir-188-5p may induce malignant progression in cancer through the inhibition of the activation of FOXN2 signaling pathway.