Oncotarget

Research Papers:

Prp19 facilitates invasion of hepatocellular carcinoma via p38 mitogen-activated protein kinase/Twist1 pathway

Jie Yin, Lan Wang, Ji-Min Zhu, Qian Yu, Ru-Yi Xue, Ying Fang, Yi-An Zhang, Yan-Jie Chen, Tao-Tao Liu, Ling Dong and Xi-Zhong Shen _

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Oncotarget. 2016; 7:21939-21951. https://doi.org/10.18632/oncotarget.7877

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Abstract

Jie Yin1,*, Lan Wang2,*, Ji-Min Zhu1, Qian Yu1, Ru-Yi Xue1, Ying Fang1, Yi-An Zhang1, Yan-Jie Chen1, Tao-Tao Liu1, Ling Dong1, Xi-Zhong Shen1,3,4

1Department of Gastroenterology, Zhongshan Hospital of Fudan University, Shanghai, China

2Department of Biochemistry and Molecular Biology, Shanghai Medical College of Fudan University, Shanghai, China

3Shanghai Institute of Liver Diseases, Zhongshan Hospital of Fudan University, Shanghai, China

4Key Laboratory of Medical Molecular Virology, Shanghai Medical College of Fudan University, Shanghai, China

*These authors have contributed equally to this work

Correspondence to:

Xi-Zhong Shen, e-mail: [email protected]

Ling Dong, e-mail: [email protected]

Keywords: liver cancer, tumor progression, ubiquitination, signaling pathway

Received: July 10, 2015    Accepted: February 20, 2016    Published: March 03, 2016

ABSTRACT

Pre-mRNA processing factor 19 (Prp19) is involved in many cellular events including pre-mRNA processing and DNA damage response. However, the pathological role of Prp19 in hepatocellular carcinoma (HCC) is still elusive. Here, we reported that Prp19 was increased in most HCC tissues and HCC cell lines, and its overexpression in HCC tissues was positively correlated with vascular invasion, tumor capsule breakthrough and poor prognosis. Prp19 potentiated migratory and invasive abilities of HCC cells in vitro and in vivo. Furthermore Prp19 facilitated Twist1-induced epithelial-mesenchymal transition. Mechanistic insights revealed that Prp19 directly binded with TGF-β-activated kinase1 (TAK1) and promoted the activation of p38 mitogen-activated protein kinase (MAPK), preventing Twist1 from degradation. Finally Prp19/p38 MAPK/Twist1 axis was attested in nude mice xenografts and HCC patient specimens. This work implies that the gain of Prp19 is a critical event during the progression of HCC, making it a promising target for malignancies with aberrant Prp19 expression.


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