title: Hoxc8 downregulates Mgl1 tumor suppressor gene expression and reduces its concomitant function on cell adhesion.
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.
authors.affiliation: Department of Anatomy, Embryology Laboratory, Brain Korea 21 Project for Medical Science, Yonsei University College of Medicine, Seoul 120-752, Korea.
authors.forename: Kalyani
authors.initials: K
authors.lastname: Ruthala
authors.forename: Jogeswar
authors.initials: J
authors.lastname: Gadi
authors.forename: Ji-Yeon
authors.initials: JY
authors.lastname: Lee
authors.forename: Heejei
authors.initials: H
authors.lastname: Yoon
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Chung
authors.forename: Myoung Hee
authors.initials: MH
authors.lastname: Kim
mesh_terms: D000818:Animals; D001212:Asialoglycoproteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D001483:Base Sequence; D002448:Cell Adhesion / Q000187:drug effects / Q000235:genetics; D002465:Cell Movement / Q000187:drug effects / Q000235:genetics; D002478:Cells, Cultured; D047369:Chromatin Immunoprecipitation; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D018507:Gene Expression Regulation, Developmental; D020868:Gene Silencing / Q000187:drug effects; D018398:Homeodomain Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D037181:Lectins, C-Type / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008297:Male; D008565:Membrane Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D034741:RNA, Small Interfering / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D001212:Asialoglycoproteins; C064720:Clec10a protein, mouse; D018398:Homeodomain Proteins; C489816:Hoxc8 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; D034741:RNA, Small Interfering