Back to Journals » Cancer Management and Research » Volume 10

LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21

Authors Xiao L, Wang Y, Liang W, Liu L, Pan N, Deng H, Li L, Zou C, Chan FL, Zhou Y

Received 17 January 2018

Accepted for publication 1 June 2018

Published 1 August 2018 Volume 2018:10 Pages 2389—2400

DOI https://doi.org/10.2147/CMAR.S162887

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Cristina Weinberg

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


Lijia Xiao,1,2,* Yuliang Wang,3,* Weicheng Liang,3 Liping Liu,4 Nannan Pan,1 Huimin Deng,1 Luqian Li,1 Chang Zou,5 Franky Leung Chan,3 Yiwen Zhou1

1Department of Clinical Laboratory Medicine, Shenzhen Hospital, Southern Medical University, Shenzhen, China; 2Department of Clinical Laboratory, Nanshan Affiliated Hospital of Guangdong Medical University, Shenzhen, China; 3School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, China; 4Department of Hepatobiliary and Pancreatic Surgery, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen, China; 5Clinical Medicine Research Center, Shenzhen Public Service Platform of Precision Medicine and Molecular Diagnosis on Tumor, The Second Clinical Medical College (Shenzhen People’s Hospital), Jinan University, Shenzhen, China

*These authors contributed equally to this work

Background: To explore potential therapeutic target is one of the areas of great interest in both clinical and basic hepatocellular carcinoma (HCC) studies. Nuclear receptor liver receptor homolog-1 (LRH-1, NR5A2) is proved to play a positive role in several cancers including breast cancer, pancreatic cancer and intestinal cancer in recent years. However, the exact role of LRH-1 in the development and progression of HCC is not fully elucidated.
Methods: The LRH-1 expression level in HCC clinical samples was examined by immunohistochemistry (IHC). Stable LRH-1-suppressed HepG2 clones (HepG2LRH-1/-) were generated by transcription activator-like effector nucleases (TALENs) and both in vitro and in vivo experiments were conducted.
Results: We confirmed that LRH-1 showed an increased expression pattern in HCC clinical samples. Our in vitro and in vivo results indicated that suppression of LRH-1 in HepG2 significantly attenuated its proliferation rate and tumorigenic capacity. Gene expression microarray analysis indicated that LRH-1mostly regulated gene expression involved in cell cycle. In addition, our gain-of-function experiments indicated that ectopic expression of LRH-1 dramatically induced the mRNA and protein levels of c-myc and cyclin E1, while attenuating the expression of p21.
Conclusion: Our results suggest that LRH-1 might be a potential therapeutic target for clinical HCC treatment.

Keywords: LRH-1, HCC, c-myc, p21, cyclin E1

Creative Commons License This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution - Non Commercial (unported, v3.0) License. By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms.

Download Article [PDF]  View Full Text [HTML][Machine readable]