Effect of the downregulation of SMYD3 expression by RNAi on RIZ1 expression and proliferation of esophageal squamous cell carcinoma

Dong,Shang-Wen; Zhang,Hao; Wang,Bao-Li; Sun,Pei; Wang,Yuan-Guo; Zhang,Peng

doi:10.3892/or.2014.3307

September-2014 Volume 32 Issue 3

Full Size Image

Journals

International Journal of Molecular Medicine

International Journal of Molecular Medicine is an international journal devoted to molecular mechanisms of human disease.

International Journal of Oncology

International Journal of Oncology is an international journal devoted to oncology research and cancer treatment.

Molecular Medicine Reports

Covers molecular medicine topics such as pharmacology, pathology, genetics, neuroscience, infectious diseases, molecular cardiology, and molecular surgery.

Oncology Reports

Oncology Reports is an international journal devoted to fundamental and applied research in Oncology.

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine is an international journal devoted to laboratory and clinical medicine.

Oncology Letters

Oncology Letters is an international journal devoted to Experimental and Clinical Oncology.

Biomedical Reports

Explores a wide range of biological and medical fields, including pharmacology, genetics, microbiology, neuroscience, and molecular cardiology.

Molecular and Clinical Oncology

International journal addressing all aspects of oncology research, from tumorigenesis and oncogenes to chemotherapy and metastasis.

World Academy of Sciences Journal

Multidisciplinary open-access journal spanning biochemistry, genetics, neuroscience, environmental health, and synthetic biology.

International Journal of Functional Nutrition

Open-access journal combining biochemistry, pharmacology, immunology, and genetics to advance health through functional nutrition.

International Journal of Epigenetics

Publishes open-access research on using epigenetics to advance understanding and treatment of human disease.

Medicine International

An International Open Access Journal Devoted to General Medicine.

September-2014 Volume 32 Issue 3

Full Size Image

Article

Effect of the downregulation of SMYD3 expression by RNAi on RIZ1 expression and proliferation of esophageal squamous cell carcinoma

Authors:
- Shang-Wen Dong
- Hao Zhang
- Bao-Li Wang
- Pei Sun
- Yuan-Guo Wang
- Peng Zhang
View Affiliations / Copyright

Affiliations: Department of Cardiothoracic Surgery, Tianjin Medical University General Hospital, Tianjin, Heping 300052, P.R. China, Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin, Heping 300070, P.R. China
Pages: 1064-1070
|
Published online on: July 3, 2014

https://doi.org/10.3892/or.2014.3307
Expand metrics +

Abstract

The present study aimed to investigate the expression and role of SET and MYND domain-containing protein 3 (SMYD3) in esophageal squamous cell carcinoma; to observe the proliferation of esophageal squamous cell carcinoma after suppression of SMYD3 expression; and to explore the effect of SMYD3 downregulation on the expression of retinoblastoma protein-interacting zinc finger gene 1 (RIZ1). Tissues from 11 patients, including cancer and normal esophageal tissues, were obtained by surgery to observe the SMYD3 protein expression immunohistochemistry. Esophageal squamous cell carcinoma TE13 cells were transfected with four different SMYD3-shRNA plasmids, and SMYD3 mRNA expression levels were assessed to select the most efficient interfering plasmid. After SMYD3 downregulation in TE13 cells, mRNA and protein expression levels of SMYD3 and RIZ1 were determined using RT-PCR and western blotting, and cell proliferation was evaluated by the MTT method. In all 11 tissue paired samples, SMYD3 protein expression was higher in the cancer tissues (72.7%; 8/11), than that in the normal tissues (18.2%; 2/11) (Fisher's exact test, P=0.03). The mRNA expression levels of SMYD3 were significantly decreased by RNA interference (P<0.05), and plasmid SMYD3-shRNA-1242 was determined to be the most effective. Compared with the controls, transfection with the SMYD3-shRNA interfering plasmid significantly reduced the SMYD3 mRNA and protein expression levels in TE13 cells (P<0.05), whereas the expression levels of the anti-oncogene RIZ1 were increased (P<0.05). The MTT assay showed that ablation of SMYD3 expression significantly inhibited proliferation of TE13 cells (P<0.05). SMYD3 may participate in the biological activity of esophageal squamous cell carcinoma, as overexpression of SMYD3 correlates with its occurrence and its downregulation inhibits cancer cell proliferation. The shRNA efficiently downregulated SMYD3 in TE13 cells, which represents an SMYD3-interfered cell-test-model for future experiments. RNAi suppression of SMYD3 promoted the expression of RIZ1 in TE13 cells, suggesting a signal transduction pathway between SMYD3 and RIZ1. The SMYD3-RIZ1 pathway may represent a therapeutic target for esophageal squamous cell carcinoma.

View Figures

View References

1	Dong SW, Ma L, Xu N, Yan HQ, Liu HY, Li YW and Zhang P: Research on the reactivation of Syk expression caused by the inhibition of DNA promoter methylation in the lung cancer. Neoplasma. 58:89–95. 2011. View Article : Google Scholar : PubMed/NCBI
2	Hamamoto R, Fumkawa Y, Morita M, et al: SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 6:731–740. 2004. View Article : Google Scholar
3	Sims RJ III and Reinberg D: From chromatin to cancer: a new histone lysine methyltransferase enters the mix. Nat Cell Biol. 6:685–687. 2004. View Article : Google Scholar : PubMed/NCBI
4	Sliva FP, Hamamoto R, Kunizaki M, et al: Enhanced methyltransferase activity of SMYD3 by the cleavage of its N-terminal region in human cancer cells. Oncogene. 27:2686–2692. 2008. View Article : Google Scholar : PubMed/NCBI
5	Chen LB, Xu JY, Yang Z and Wang GB: Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration. World J Gastroenterol. 13:5718–5724. 2007. View Article : Google Scholar : PubMed/NCBI
6	Kunizaki M, Hamamoto R, Silva FP, Yamaguchi K, Nagayasu T, Shibuya M, Nakamura Y and Furukawa Y: The lysine 831 of vascular endothelial growth factor receptor 1 is a novel target of methylation by SMYD3. Cancer Res. 67:10759–10765. 2007. View Article : Google Scholar : PubMed/NCBI
7	Liu C, Fang X, Ge Z, et al: The telomerase reverse transcriptase (hTERT) gene is a direct target of the histone methyltransferase SMYD3. Cancer Res. 67:2626–2631. 2007. View Article : Google Scholar
8	Luo XG, Xi T, Guo S, et al: Effects of SMYD3 overexpression on transformation, serum dependence, and apoptosis sensitivity in NIH3T3 cells. IUBMB Life. 61:679–684. 2009. View Article : Google Scholar : PubMed/NCBI
9	Buyse IM, Shao G and Huang S: The retinoblastoma protein binds to RIZ, a zinc-finger protein that shares an epitope with the adenovirus E1A protein. Proc Natl Acad Sci USA. 92:4467–4471. 1995. View Article : Google Scholar : PubMed/NCBI
10	Steele-Perkins G, Fang W, Yang XH, et al: Tumor formation and inactivation of RIZ1, an Rb-binding member of a nuclear protein-methyltransferase superfamily. Genes Dev. 15:2250–2262. 2001. View Article : Google Scholar : PubMed/NCBI
11	Robert MF, Morin S, Beaulieu N, Gauthier F, Chute IC, Barsalou A and MacLeod AR: DNMT1 is required to maintain CpG methylation and aberrant gene silencing in human cancer cells. Nat Genet. 33:61–65. 2003. View Article : Google Scholar : PubMed/NCBI
12	Dong SW, Cui YT, Zhong RR, Liang DC, Liu YM, Wang YG, He Z, Wang S, Liang SJ and Zhang P: Decreased expression of retinoblastoma protein-interacting zinc-finger gene 1 in human esophageal squamous cell cancer by DNA methylation. Clin Lab. 58:41–51. 2012.PubMed/NCBI
13	Dong SW, Zhang P, Liu YM, et al: 2012 Study on RIZ1 gene promoter methylation status in human esophageal squamous cell carcinoma. World J Gastroenterol. 18:576–582. 2012.
14	Dong SW, Li D, Xu C, Sun P, Wang YG and Zhang P: Alteration in gene expression profile and oncogenicity of esophageal squamous cell carcinoma by RIZ1 upregulation. World J Gastroenterol. 19:6170–6177. 2013. View Article : Google Scholar : PubMed/NCBI
15	Dong S, Zhang P, Liang S, Wang S, Sun P and Wang Y: The role of the retinoblastoma protein-interacting zinc finger gene 1 tumor suppressor gene in human esophageal squamous cell carcinoma cells. Oncol Lett. 6:1656–1662. 2013.PubMed/NCBI
16	Sasaki O, Meguro K, Tohmiya Y, et al: Altered expression or retinoblastoma protein-interacting zinc finger, RIZ, in human leukemia. Br J Haematol. 119:940–948. 2002. View Article : Google Scholar : PubMed/NCBI

Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Effect of the downregulation of SMYD3 expression by RNAi on RIZ1 expression and proliferation of esophageal squamous cell carcinoma

This article is mentioned in:

Abstract

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

Figure 6

Related Articles