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
Checked for plagiarism Yes
Review by Single-blind
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
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