Li-Bo Chen1, Jun-Yao Xu, Zhen Yang, Guo-Bin Wang. 1. Hepatobiliary center, Union Hospital of Huazhong University of Science and Technology, Wuhan 430022, Hubei province, China. libo_chen@hotmail.com
Abstract
AIM: To investigate the role of SMYD3 in hepatocellular carcinoma (HCC) development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS: Expression of SMYD3 in HCC cell lines and tissues were measured; silencing of SMYD3 by RNA interference (RNAi) was effectuated, hepatoma cell proliferation, migration and apoptosis were tested, with RIZ1 CpG promoter methylation, and corresponding mRNA expression were investigated. RESULTS: SMYD3 over-expression in HCC was associated with RIZ1 hypermethylation and mRNA down-expression. Suppression of SMYD3 expression de-methylated RIZ1 CpG promoter (P < 0.01) and increased RIZ1 mRNA expression (P < 0.01). Consequently, SMYD3 down-expression with RIZ1 de-methylation strongly inhibited hepatoma cell growth (MTT inhibitory rates: Pgenesil-1-s1 60.95% +/- 7.97%, Pgenesil-1-s2 72.14% +/- 9.68% vs Pgenesil-1-hk 6.89% +/- 4.12%, P < 0.01) and migration (Pgenesil-1-s1 4.24% +/- 1.58%, Pgenesil-1-s1 4.87% +/- 0.73% vs Pgenesil-1 19.03% +/- 4.63%, Pgenesil-1-hk 19.95% +/- 5.21%, P < 0.01) and induced apoptosis (FCM subG1 phase Pgenesil-1-s1 19.07% +/- 1.78%, Pgenesil-1-s2 17.68% +/- 2.36% vs Pgenesil-1 0.47% +/- 0.12%, Pgenesil-1-hk 1.46% +/- 0.28%, P < 0.01. TUNEL-positive cells: Pgenesil-1-s1 40.24% +/- 5.18%, Pgenesil-1-s2 38.48% +/- 4.65% vs Pgenesil-1 2.18% +/- 1.34%, Pgenesil-1-hk 2.84% +/- 1.22%, P < 0.01) in HepG2 cells. CONCLUSION: These results demonstrate that SMYD3 plays a critical role in the carcinogenesis and progression of HCC. The proliferation, migration induction and apoptosis inhibition activities of SMYD3 may be mediated through RIZ1 CpG promoter hypermethylation.
AIM: To investigate the role of SMYD3 in hepatocellular carcinoma (HCC) development and progression and to verify whether its regulation activity was through RIZ1 inactivation. METHODS: Expression of SMYD3 in HCC cell lines and tissues were measured; silencing of SMYD3 by RNA interference (RNAi) was effectuated, hepatoma cell proliferation, migration and apoptosis were tested, with RIZ1 CpG promoter methylation, and corresponding mRNA expression were investigated. RESULTS:SMYD3 over-expression in HCC was associated with RIZ1 hypermethylation and mRNA down-expression. Suppression of SMYD3 expression de-methylated RIZ1 CpG promoter (P < 0.01) and increased RIZ1 mRNA expression (P < 0.01). Consequently, SMYD3 down-expression with RIZ1 de-methylation strongly inhibited hepatoma cell growth (MTT inhibitory rates: Pgenesil-1-s1 60.95% +/- 7.97%, Pgenesil-1-s2 72.14% +/- 9.68% vs Pgenesil-1-hk 6.89% +/- 4.12%, P < 0.01) and migration (Pgenesil-1-s1 4.24% +/- 1.58%, Pgenesil-1-s1 4.87% +/- 0.73% vs Pgenesil-1 19.03% +/- 4.63%, Pgenesil-1-hk 19.95% +/- 5.21%, P < 0.01) and induced apoptosis (FCM subG1 phase Pgenesil-1-s1 19.07% +/- 1.78%, Pgenesil-1-s2 17.68% +/- 2.36% vs Pgenesil-1 0.47% +/- 0.12%, Pgenesil-1-hk 1.46% +/- 0.28%, P < 0.01. TUNEL-positive cells: Pgenesil-1-s1 40.24% +/- 5.18%, Pgenesil-1-s2 38.48% +/- 4.65% vs Pgenesil-1 2.18% +/- 1.34%, Pgenesil-1-hk 2.84% +/- 1.22%, P < 0.01) in HepG2 cells. CONCLUSION: These results demonstrate that SMYD3 plays a critical role in the carcinogenesis and progression of HCC. The proliferation, migration induction and apoptosis inhibition activities of SMYD3 may be mediated through RIZ1 CpG promoter hypermethylation.
Authors: Miguel Alaminos; Verónica Dávalos; Santiago Ropero; Fernando Setién; Maria F Paz; Michel Herranz; Mario F Fraga; Jaume Mora; Nai-Kong V Cheung; William L Gerald; Manel Esteller Journal: Cancer Res Date: 2005-04-01 Impact factor: 12.701
Authors: N Kondoh; T Wakatsuki; A Ryo; A Hada; T Aihara; S Horiuchi; N Goseki; O Matsubara; K Takenaka; M Shichita; K Tanaka; M Shuda; M Yamamoto Journal: Cancer Res Date: 1999-10-01 Impact factor: 12.701