Oncotarget

Research Papers:

Zinc finger protein ZBTB20 is an independent prognostic marker and promotes tumor growth of human hepatocellular carcinoma by repressing FoxO1

Heping Kan, Yuqi Huang _, Xianghong Li, Dingli Liu, Jianjia Chen and Miaojiang Shu

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Oncotarget. 2016; 7:14336-14349. https://doi.org/10.18632/oncotarget.7425

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Abstract

Heping Kan1, Yuqi Huang1, Xianghong Li1, Dingli Liu2, Jianjia Chen1, Miaojiang Shu1

1Department of Hepatobiliary Surgery, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

2Department of Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Correspondence to:

Yuqi Huang, e-mail: [email protected]

Keywords: ZBTB20, FoxO1, hepatocellular carcinoma, proliferation, cell cycle

Received: September 27, 2015     Accepted: January 29, 2016     Published: February 16, 2016

ABSTRACT

Zinc finger and BTB domain-containing 20 (ZBTB20) is a new BTB/POZ-domain gene and a member of the POK family of transcriptional repressors. Notably, the role of ZBTB20 and its underlying mechanisms involved in hepatocarcinogenesis are poorly investigated. In this study, the expression of ZBTB20 was significantly overexpressed in hepatocellular carcinoma (HCC) tissues. The positive expression of ZBTB20 was associated with large tumor size, high Edmondson-Steiner grading and advanced tumor-node-metastasis (TNM) tumor stage. Additionally, HCC patients with positive expression of ZBTB20 had a poorer 5-year survival. Multivariate analyses revealed that ZBTB20 overexpression was an independent prognostic factor for HCC. Gain- and loss-of-function experiments demonstrated that ZBTB20 promoted HCC cell viability, proliferation, tumorigenicity, and cell cycle progression. Mechanistically, Cyclin D1 and Cyclin E were increased, while p21 and p27 were decreased by ZBTB20 in HCC cells. FoxO1 was inversely correlated with ZBTB20 protein expression in the same cohort of HCC specimens. We further revealed that FoxO1 was transcriptionally repressed by ZBTB20 in HCC. Moreover, restoration of FoxO1 expression partially abrogated ZBTB20-induced HCC cell proliferation and growth entry in vitro and in vivo. Collectively, these results indicate that ZBTB20 may serve as a prognostic marker and promotes tumor growth of HCC via transcriptionally repressing FoxO1.


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