title: GATA4 promotes hepatoblastoma cell proliferation by altering expression of miR125b and DKK3.
abstract: GATA4 is a zinc finger DNA-binding protein that plays an important role in mammalian liver development. However, the effects of GATA4 in hepatoblastoma (HB), a common liver cancer in pediatric patients, remain largely unknown. In this study, we demonstrate that GATA4 promotes growth and survival in the Huh6 human hepatoblastoma cell line. GATA4 expression was high in Huh6 cells, and its knockdown decreased expression of Dickkopf-related protein 3 (DKK3), a gene that may contribute to premature or undifferentiated phenotypes in HB. GATA4 also directly bound to the promoter regions of the miRNA miR125b and inhibited its expression in Huh6 cells. DKK3 was a direct target of miR125b in Huh6 cells. Inhibition of miR125b or overexpression of DKK3 promoted proliferation, survival, migration, and invasion in Huh6 cells. This is the first report to demonstrate that GATA4 promotes oncogenesis by inhibiting miR125b-dependent suppression of DKK3 expression. This GATA4/miR125b/DKK3 axis may be a major regulator of growth, migration, invasion, and survival in hepatoma cells, and is therefore a potential therapeutic target or biomarker for progression in HB patients.
authors: Central Laboratory, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors: Yihua
authors: Y
authors: Pei
authors: Central Laboratory, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors: Qin
authors: Q
authors: Yao
authors: Department of Gastrointestinal Surgery, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors: Sibo
authors: S
authors: Yuan
authors: Department of Spine Surgery, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors: Bozhen
authors: B
authors: Xie
authors: Department of Pathology, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors: Yan
authors: Y
authors: Liu
authors: Department Otolaryngology, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors: Chunsheng
authors: C
authors: Ye
authors: Department of Gastrointestinal Surgery, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China.
authors: Huiqin
authors: H
authors: Zhuo
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology; D018925:Chemokines; D005260:Female; D050991:GATA4 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D056945:Hep G2 Cells; D018197:Hepatoblastoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D008113:Liver Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D035683:MicroRNAs / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014162:Transfection
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018925:Chemokines; C498624:DKK3 protein, human; D050991:GATA4 Transcription Factor; C484170:GATA4 protein, human; D036341:Intercellular Signaling Peptides and Proteins; C531888:MIRN125 microRNA, human; D035683:MicroRNAs
keywords: DKK3; GATA4; hepatoblastoma; miR125b