Basic Research
Copyright ©2007 Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 21, 2007; 13(43): 5718-5724
Published online Nov 21, 2007. doi: 10.3748/wjg.v13.i43.5718
Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration
Li-Bo Chen, Jun-Yao Xu, Zhen Yang, Guo-Bin Wang
Li-Bo Chen, Guo-Bin Wang, Hepatobiliary center, Union Hospital of Huazhong University of Science & Technology, Wuhan 430022, Hubei province, China
Jun-Yao Xu, Department of General Surgery, The Second Affiliated Hospital of Sun Yat-seu University, Guangzhou 510120, Guangdong province, China
Zhen Yang, Department of integrated surgery, Tongji Hospital of Huazhong University of Science & Technology, Wuhan 430030, Hubei province, China
Author contributions: All authors contributed equally to the work.
Supported by National Natural Science Foundation of China, No 30200273 & 30672067
Correspondence to: Li-Bo Chen, Hepatobiliary center, Union Hospital of Huazhong University of Science and Technology, Wuhan 430022, Hubei province, China.
Telephone: +86-27-85351623 Fax: +86-27-85776343
Received: April 4, 2007
Revised: July 31, 2007
Accepted: September 14, 2007
Published online: November 21, 2007

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.

Keywords: SMYD3, Hepatocellular carcinoma, Retinoblastoma protein-interacting zinc finger gene, Histone methyltransferase, DNA methylation