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PRMT5 is a potential oncoprotein that upregulates G1 cyclins/CDKs and the PI3K/AKT signaling cascade.
MedLine Citation:
PMID:  22726390     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Increasing evidence suggests that PRMT5, a protein arginine methyltransferase, is involved in tumorigenesis. However, no systematic research has demonstrated the cell-transforming activity of PRMT5. We investigated the involvement of PRMT5 in tumor formation. First, we showed that PRMT5 was associated with many human cancers, through statistical analysis of microarray data in the NCBI GEO database. Overexpression of ectopic PRMT5 per se or its specific shRNA enhanced or reduced cell growth under conditions of normal or low concentrations of serum, low cell density, and poor cell attachment. A stable clone that expressed exogenous PRMT5 formed tumors in nude mice, which demonstrated that PRMT5 is a potential oncoprotein. PRMT5 accelerated cell cycle progression through G1 phase and modulated regulators of G1; for example, it upregulated cyclin-dependent kinase (CDK) 4, CDK6, and cyclins D1, D2 and E1, and inactivated retinoblastoma protein (Rb). Moreover, PRMT5 activated phosphoinositide 3-kinase (PI3K)/AKT and suppressed c-Jun N-terminal kinase (JNK)/c-Jun signaling cascades. However, only inhibition of PI3K activity, and not overexpression of JNK, blocked PRMT5-induced cell proliferation. Further analysis of PRMT5 expression in 64 samples of human lung cancer tissues by microarray and western blot analysis revealed a tight association of PRMT5 with lung cancer. Knockdown of PRMT5 retarded cell growth of lung cancer cell lines A549 and H1299. In conclusion, to the best of our knowledge, we have characterized the cell-transforming activity of PRMT5 and delineated its underlying mechanisms for the first time.
Authors:
Tong-You Wade Wei; Chi-Chang Juan; Jiun-Yi Hsia; Li-Jen Su; Yuan-Chii Gladys Lee; Hsiang-Yun Chou; Jo-Mei Maureen Chen; Yu-Chung Wu; Shao-Chih Chiu; Chung-Ping Hsu; Kuo-Lin Liu; Chang-Tze Ricky Yu
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-24
Journal Detail:
Title:  Cancer science     Volume:  -     ISSN:  1349-7006     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-6-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101168776     Medline TA:  Cancer Sci     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2012 Japanese Cancer Association.
Affiliation:
Graduate Institute of Biomedicine and Biomedical Technology, National Chi Nan University, Puli, Nantou, 545, Taiwan.
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