Oncotarget

Research Papers:

GATA4 promotes hepatoblastoma cell proliferation by altering expression of miR125b and DKK3

Yihua Pei _, Qin Yao, Sibo Yuan, Bozhen Xie, Yan Liu, Chunsheng Ye and Huiqin Zhuo

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Oncotarget. 2016; 7:77890-77901. https://doi.org/10.18632/oncotarget.12839

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Abstract

Yihua Pei1,*, Qin Yao1,*, Sibo Yuan2, Bozhen Xie3, Yan Liu4, Chunsheng Ye5, Huiqin Zhuo2

1Central Laboratory, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China

2Department of Gastrointestinal Surgery, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China

3Department of Spine Surgery, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China

4Department of Pathology, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China

5Department Otolaryngology, The Affiliated Zhongshan Hospital, Xiamen University, Xiamen, Fujian 361004, China

*These authors have contributed equally to this work

Correspondence to:

Yihua Pei, email: [email protected]

Huiqin Zhuo, email: [email protected]

Keywords: hepatoblastoma, GATA4, miR125b, DKK3

Received: January 19, 2016    Accepted: October 14, 2016    Published: October 24, 2016

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.


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