Hoxc8 downregulates Mgl1 tumor suppressor gene expression and reduces its concomitant function on cell adhesion
Dept. of Medical Science/박사
Hoxc8 is a homeobox gene family member, which is essential for growth and differentiation during development. Mgl1, a mouse homologue of the Drosophila tumor suppressor gene lgl, was previously identified as a possible target of Hoxc8. However, the biological effects and underlying molecular mechanism of Hoxc8 regulation on Mgl1 has not been fully established. The expression pattern of Hoxc8 was inversely correlated with that of Mgl1 in different cells and tissues. In this study, we showed that Hoxc8 overexpression downregulates the Mgl1 mRNA expression. Characterization of the ~2 kb Mgl1 promoter region revealed that theupstream sequence contains several putative Hox core binding sites. Chromatin mmunoprecipitation assay confirmed that Hoxc8 directly binds to the 5′ upstream region of Mgl1. The promoter activity of this region was diminished by Hoxc8 expression but resumed by knockdown of Hoxc8 using siRNA against Hoxc8. Functional study of Mgl1 in C3H10T1/2 cells revealed a significant reduction in cell adhesion upon expression of Hoxc8 without any effect on cell morphology. Taken together, the data suggest that Hoxc8 down regulates Mgl1 expression via direct binding to the promoter region, which in turn reduces cell adhesion.