Oncotarget

Research Papers:

JARID1B promotes metastasis and epithelial-mesenchymal transition via PTEN/AKT signaling in hepatocellular carcinoma cells

Bo Tang, Guangying Qi, Fang Tang, Shengguang Yuan, Zhenran Wang, Xingsi Liang, Bo Li, Shuiping Yu, Jie Liu, Qi Huang, Yangchao Wei, Run Zhai, Biao Lei, Hongping Yu, Xingyuan Jiao and Songqing He _

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Oncotarget. 2015; 6:12723-12739. https://doi.org/10.18632/oncotarget.3713

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Abstract

Bo Tang1,2, Guangying Qi2,3, Fang Tang1,2, Shengguang Yuan1,2, Zhenran Wang1,2, Xingsi Liang1,2, Bo Li1,2, Shuiping Yu1,2, Jie Liu1,2, Qi Huang1,2, Yangchao Wei1,2, Run Zhai1,2, Biao Lei1,2, Hongping Yu4, Xingyuan Jiao5 and Songqing He1,2

1 Department of Hepatobiliary Surgery, Guilin Medical University, Affiliated Hospital, Guilin, Guangxi, People’s Republic of China

2 Laboratory of Liver Injury and Repair Molecular Medicine, Guilin Medical University, Guilin, Guangxi, People’s Republic of China

3 Department of Pathology and Physiopathology, Guilin Medical University, Guilin, Guangxi, People’s Republic of China

4 Department of Epidemiology and Statistics, School of Public Health, Guilin Medical College, Guilin, Guangxi, People’s Republic of China

5 Department of General Surgery, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou, People’s Republic of China

Correspondence to:

Songqing He, email:

Xingyuan Jiao, email:

Keywords: JARID1B, metastasis, epithelial-mesenchymal transition, invasion, PTEN

Received: February 16, 2015 Accepted: March 10, 2015 Published: March 30, 2015

Abstract

JARID1B is a member of the family of JmjC domain-containing proteins that removes methyl residues from methylated lysine 4 on histone H3 lysine 4 (H3K4). JARID1B has been proposed as an oncogene in many types of tumors; however, its role and underlying mechanisms in hepatocellular carcinoma (HCC) remain unknown. Here we show that JARID1B is elevated in HCC and its expression level is positively correlated with metastasis. In addition Kaplan-Meier survival analysis showed that high expression of JARID1B was associated with decreased overall survival of HCC patients. Overexpression of JARID1B in HCC cells increased proliferation, epithelial-mesenchymal transition, migration and invasion in vitro, and enhanced tumorigenic and metastatic capacities in vivo. In contrast, silencing JARID1B in aggressive and invasive HCC cells inhibited these processes. Mechanistically, we found JARID1B exerts its function through modulation of H3K4me3 at the PTEN gene promoter, which was associated with inactive PTEN transcription. PTEN overexpression blocked JARID1B-driven proliferation, EMT, and metastasis. Our results, for the first time, portray a pivotal role of JARID1B in stimulating metastatic behaviors of HCC cells. Targeting JARID1B may thus be a useful strategy to impede HCC cell invasion and metastasis.


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