Abstract

Hepatocellular carcinoma (HCC) is the third leading cause of cancer related death worldwide; however, the molecular mechanisms regulating HCC progression remain largely unknown. In this study, we determined the role of DDX39 which a DEAD-box RNA helicase in HCC progression, and found DDX39 was upregulated in HCC tissues and cells, DDX39 expression was positive correlated with advanced clinical stage, survival analysis showed patients with high-DDX39 levels had poor outcome, it was an independent prognostic factor. Functional analysis revealed that DDX39 overexpression promoted HCC cell migration, invasion, growth, and metastasis, DDX39 knockdown inhibited HCC cell migration, invasion, growth, and metastasis. Mechanism analysis suggested DDX39 overexpression increased β-catenin expression in nucleus and increased Wnt/β-catenin pathway target genes levels, while DDX39 knockdown reduced this effect. Knockdown of Wnt/β-catenin pathway co-activators TCF4 and LEF1 in DDX39 overexpressing HCC cells inhibited Wnt/β-catenin pathway target genes. The invasion ability was also reduced, confirming DDX39 regulates HCC progression by activating Wnt/β-catenin pathway. In conclusion, we found DDX39 is a target and prognostic factor for HCC, and promotes HCC migration, invasion, growth, and metastasis by activating Wnt/β-catenin pathway.

Details

Title
DDX39 promotes hepatocellular carcinoma growth and metastasis through activating Wnt/β-catenin pathway
Author
Zhang, Tong 1 ; Ma Zhenjiang 2 ; Liu, Lijuan 3 ; Sun, Jian 4 ; Tang, Hui 1 ; Zhang, Bing 5 ; Zou Ying 6 ; Li, Heping 6 

 the Third Affiliated Hospital of Sun Yat-sen University, Department of Hepatic Surgery, Liver Transplant Center, Guangzhou, China (GRID:grid.412558.f) (ISNI:0000 0004 1762 1794); Liver Transplantation Center of Sun Yat-sen University, Guangzhou, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X); Organ Transplantation Institute of Guangdong Province, Guangzhou, China (GRID:grid.12981.33) 
 the First Affiliated Hospital of Sun Yat-sen University, Department of Interventional Radiology, Guangzhou, China (GRID:grid.412615.5) (ISNI:0000 0004 1803 6239) 
 Sun Yat-Sen University, Department of Cardiology, the First Affiliated Hospital, Guangzhou, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X) 
 Sun Yat-Sen University, Department of Hepatobiliary and pancreatic Surgery, Sun Yat-Sen Memorial Hospital, Guangzhou, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X); Sun Yat-Sen University, Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Medical Research Center, Sun Yat-Sen Memorial Hospital, Guangzhou, China (GRID:grid.12981.33) (ISNI:0000 0001 2360 039X) 
 the First Affiliated Hospital of Sun Yat-sen University, Department of Medical Imaging, Guangzhou, China (GRID:grid.412615.5) (ISNI:0000 0004 1803 6239) 
 the First Affiliated Hospital of Sun Yat-sen University, Department of Medical Oncology, Guangzhou, China (GRID:grid.412615.5) (ISNI:0000 0004 1803 6239) 
Publication year
2018
Publication date
Jun 2018
Publisher
Springer Nature B.V.
e-ISSN
20414889
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2621101968
Copyright
© The Author(s) 2018. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.