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- Title
LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21.
- Authors
Xiao, Lijia; Wang, Yuliang; Liang, Weicheng; Liu, Liping; Pan, Nannan; Deng, Huimin; Li, Luqian; Zou, Chang; Chan, Franky Leung; Zhou, Yiwen
- Abstract
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.
- Subjects
LIVER cancer; CYCLIN E; NUCLEAR receptors (Biochemistry); CANCER treatment; GENE expression
- Publication
Cancer Management & Research, 2018, Vol 10, p2389
- ISSN
1179-1322
- Publication type
Article
- DOI
10.2147/CMAR.S162887