Title |
LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21
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Published in |
Cancer Management and Research, August 2018
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DOI | 10.2147/cmar.s162887 |
Pubmed ID | |
Authors |
Lijia Xiao, Yuliang Wang, Weicheng Liang, Liping Liu, Nannan Pan, Huimin Deng, Luqian Li, Chang Zou, Franky Leung Chan, Yiwen Zhou |
Abstract |
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. The LRH-1 expression level in HCC clinical samples was examined by immunohis-tochemistry (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. 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. Our results suggest that LRH-1 might be a potential therapeutic target for clinical HCC treatment. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 27 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Master | 6 | 22% |
Student > Bachelor | 3 | 11% |
Researcher | 3 | 11% |
Student > Ph. D. Student | 2 | 7% |
Lecturer | 1 | 4% |
Other | 4 | 15% |
Unknown | 8 | 30% |
Readers by discipline | Count | As % |
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Chemistry | 2 | 7% |
Social Sciences | 1 | 4% |
Other | 1 | 4% |
Unknown | 8 | 30% |