Hoxc8 downregulates Mgl1 tumor suppressor gene expression and reduces its concomitant function on cell adhesion |
| |
Authors: | Kalyani Ruthala Jogeswar Gadi Ji-Yeon Lee Heejei Yoon Hyun Joo Chung Myoung Hee Kim |
| |
Institution: | (1) Department of Anatomy, Embryology Lab, Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, 134 Seodaemun-gu, Shinchon-dong, 120-752 Seoul, South Korea;(2) College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, China;(3) Brain Korea 21 Project for Medical Science, College of Medicine, Yonsei University, Seoul, 120-752, South Korea;(4) Center for Drug Discovery Technologies, Korea Research Institute of Chemical Technology, Daejeon, South Korea; |
| |
Abstract: | Hoxc8 is a homeobox gene family member, which is essential for growth and differentiation. 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 endogenous expression patterns of Hoxc8 were inversely correlated with those of Mgl1 in different types of cells and tissues. Here we showed that Hoxc8 overexpression downregulated the Mgl1 mRNA expression. Characterization of the ∼2 kb Mgl1 promoter region revealed that the upstream sequence contains several putative Hox core binding sites and chromatin immunoprecipitation
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. Taken together, our data suggest that Hoxc8 downregulates Mgl1 expression via direct binding to the promoter region, which in turn reduces cell adhesion and concomitant cell migration. |
| |
Keywords: | cell adhesion direct downstream target gene Hoxc8 Mgl1 tumor suppressor |
本文献已被 PubMed SpringerLink 等数据库收录! |
|