LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21
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...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2018-08-01
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| Series: | Cancer Management and Research |
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| Online Access: | https://www.dovepress.com/lrh-1-drives-hepatocellular-carcinoma-partially-through-induction-of-c-peer-reviewed-article-CMAR |
| _version_ | 1818303310314078208 |
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| author | Xiao L Wang Y Liang W Liu L Pan N Deng H Li L Zou C Chan FL Zhou Y |
| author_facet | Xiao L Wang Y Liang W Liu L Pan N Deng H Li L Zou C Chan FL Zhou Y |
| author_sort | Xiao L |
| collection | DOAJ |
| description | 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 |
| first_indexed | 2024-12-13T05:52:46Z |
| format | Article |
| id | doaj.art-4c8062e462f449c6a08c8b44b74de4ad |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-13T05:52:46Z |
| publishDate | 2018-08-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-4c8062e462f449c6a08c8b44b74de4ad2022-12-21T23:57:30ZengDove Medical PressCancer Management and Research1179-13222018-08-01Volume 102389240039615LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21Xiao LWang YLiang WLiu LPan NDeng HLi LZou CChan FLZhou YLijia 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 E1https://www.dovepress.com/lrh-1-drives-hepatocellular-carcinoma-partially-through-induction-of-c-peer-reviewed-article-CMARLRH-1；HCC；c-myc；p21；cyclinE1 |
| spellingShingle | Xiao L Wang Y Liang W Liu L Pan N Deng H Li L Zou C Chan FL Zhou Y LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21 Cancer Management and Research LRH-1；HCC；c-myc；p21；cyclinE1 |
| title | LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21 |
| title_full | LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21 |
| title_fullStr | LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21 |
| title_full_unstemmed | LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21 |
| title_short | LRH-1 drives hepatocellular carcinoma partially through induction of c-myc and cyclin E1, and suppression of p21 |
| title_sort | lrh 1 drives hepatocellular carcinoma partially through induction of c myc and cyclin e1 and suppression of p21 |
| topic | LRH-1；HCC；c-myc；p21；cyclinE1 |
| url | https://www.dovepress.com/lrh-1-drives-hepatocellular-carcinoma-partially-through-induction-of-c-peer-reviewed-article-CMAR |
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