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Published in: Tumor Biology 6/2015

01-06-2015 | Research Article

Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer

Authors: Yong Liu, Honggen Liu, Xuegang Luo, Jingyu Deng, Yuan Pan, Han Liang

Published in: Tumor Biology | Issue 6/2015

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Abstract

SET and MYND domain-containing protein 3 (SMYD3) plays a key role in the progression of human cancer. Matrix metalloproteinase (MMP)-9 is being related to tumor progression. It has been reported that SMYD3 and MMP-9 are overexpressed in human cancers. However, the exact roles of SMYD3 and MMP-9 in the metastasis and prognosis of gastric cancer (GC) remain unclear. The expressions of SMYD3 and MMP-9 were detected by semiquantitative reverse transcription polymerase chain reaction and Western blotting in gastric cancer and adjacent nontumor tissues. In addition, SMYD3 and MMP-9 expressions were analyzed by immunohistochemistry in formalin-fixed samples from 186 gastric cancer patients. The messenger RNA (mRNA) and protein expression levels of SMYD3 and MMP-9 in gastric cancer tissues were both significantly higher than those in adjacent nontumor tissues. In addition, the expression of SMYD3 was correlated with size of primary tumor and lymph node metastasis, while size of primary tumor and serosal invasion were identified as the independently relative factors of MMP-9 expression in GC tissues. SMYD3 expression and MMP-9 expression in GC tissues were significantly and positively correlated. Multivariate analysis results demonstrated that degree of differentiation, lymph node metastasis, TNM stage, SMYD3 expression, and MMP-9 expression were the independent prognostic indicators of gastric cancer. SMYD3 and MMP-9 may play important roles in tumor invasion, metastasis, and prognosis and could work as promising targets for prognostic prediction in gastric cancer.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ. Cancer statistics, 2009. CA Cancer J Clin. 2009;59:225–49.CrossRefPubMed
3.
go back to reference Van Aller GS, Reynoird N, Barbash O, Huddleston M, Liu S, Zmoos AF, et al. Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics. 2012;7:340–3.CrossRefPubMedPubMedCentral Van Aller GS, Reynoird N, Barbash O, Huddleston M, Liu S, Zmoos AF, et al. Smyd3 regulates cancer cell phenotypes and catalyzes histone H4 lysine 5 methylation. Epigenetics. 2012;7:340–3.CrossRefPubMedPubMedCentral
4.
go back to reference Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, et al. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004;6:731–40.CrossRefPubMed Hamamoto R, Furukawa Y, Morita M, Iimura Y, Silva FP, Li M, et al. SMYD3 encodes a histone methyltransferase involved in the proliferation of cancer cells. Nat Cell Biol. 2004;6:731–40.CrossRefPubMed
5.
go back to reference Luo XG, Xi T, Guo S, Liu ZP, Wang N, Jiang Y, et al. Effects of SMYD3 overexpression on transformation, serum dependence, and apoptosis sensitivity in NIH3T3 cells. IUBMB Life. 2009;61:679–84.CrossRefPubMed Luo XG, Xi T, Guo S, Liu ZP, Wang N, Jiang Y, et al. Effects of SMYD3 overexpression on transformation, serum dependence, and apoptosis sensitivity in NIH3T3 cells. IUBMB Life. 2009;61:679–84.CrossRefPubMed
6.
go back to reference Chen LB, Xu JY, Yang Z. Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration. World J Gastroenterol. 2007;13:5718–24.CrossRefPubMedPubMedCentral Chen LB, Xu JY, Yang Z. Silencing SMYD3 in hepatoma demethylates RIZI promoter induces apoptosis and inhibits cell proliferation and migration. World J Gastroenterol. 2007;13:5718–24.CrossRefPubMedPubMedCentral
7.
go back to reference Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y, et al. Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci. 2006;97:113–8.CrossRefPubMed Hamamoto R, Silva FP, Tsuge M, Nishidate T, Katagiri T, Nakamura Y, et al. Enhanced SMYD3 expression is essential for the growth of breast cancer cells. Cancer Sci. 2006;97:113–8.CrossRefPubMed
8.
go back to reference Liu Y, Luo X, Deng J, Pan Y, Zhang L, Liang H. SMYD3 overexpression was a risk factor in the biological behavior and prognosis of gastric carcinoma. Tumour Biol. 2014. doi:10.1007/s13277-014-2891-z. Liu Y, Luo X, Deng J, Pan Y, Zhang L, Liang H. SMYD3 overexpression was a risk factor in the biological behavior and prognosis of gastric carcinoma. Tumour Biol. 2014. doi:10.​1007/​s13277-014-2891-z.
9.
go back to reference Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 1980;284:67–8.CrossRefPubMed Liotta LA, Tryggvason K, Garbisa S, Hart I, Foltz CM, Shafie S. Metastatic potential correlates with enzymatic degradation of basement membrane collagen. Nature. 1980;284:67–8.CrossRefPubMed
10.
go back to reference Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer. 2000;36:1621–30.CrossRefPubMed Curran S, Murray GI. Matrix metalloproteinases: molecular aspects of their roles in tumour invasion and metastasis. Eur J Cancer. 2000;36:1621–30.CrossRefPubMed
11.
go back to reference Stetler-Stevenson WG. The role of matrix metalloproteinases in tumor invasion, metastasis and angiogenesis. Surg Oncol Clin N Am. 2001;10:383–92.PubMed Stetler-Stevenson WG. The role of matrix metalloproteinases in tumor invasion, metastasis and angiogenesis. Surg Oncol Clin N Am. 2001;10:383–92.PubMed
12.
go back to reference Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997;89:1260–70.CrossRefPubMed Chambers AF, Matrisian LM. Changing views of the role of matrix metalloproteinases in metastasis. J Natl Cancer Inst. 1997;89:1260–70.CrossRefPubMed
13.
go back to reference Curran S, Dundas SR, Buxton J, Leeman MF, Ramsay R, Murray GI. Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. Clin Cancer Res. 2004;10:8229–34.CrossRefPubMed Curran S, Dundas SR, Buxton J, Leeman MF, Ramsay R, Murray GI. Matrix metalloproteinase/tissue inhibitors of matrix metalloproteinase phenotype identifies poor prognosis colorectal cancers. Clin Cancer Res. 2004;10:8229–34.CrossRefPubMed
14.
go back to reference Wang W, McLeod HL, Cassidy J. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int J Cancer. 2003;104:504–11.CrossRefPubMed Wang W, McLeod HL, Cassidy J. Disulfiram-mediated inhibition of NF-kappaB activity enhances cytotoxicity of 5-fluorouracil in human colorectal cancer cell lines. Int J Cancer. 2003;104:504–11.CrossRefPubMed
15.
go back to reference Tamatani T, Azuma M, Ashida Y, Motegi K, Takashima R, Harada K, et al. Enhanced radiosensitization and chemosensitization in NF-kappaB suppressed human oral cancer cells via the inhibition of gamma-irradiation- and 5-FU-induced production of IL-6 and IL-8. Int J Cancer. 2004;108:912–21.CrossRefPubMed Tamatani T, Azuma M, Ashida Y, Motegi K, Takashima R, Harada K, et al. Enhanced radiosensitization and chemosensitization in NF-kappaB suppressed human oral cancer cells via the inhibition of gamma-irradiation- and 5-FU-induced production of IL-6 and IL-8. Int J Cancer. 2004;108:912–21.CrossRefPubMed
16.
go back to reference Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol. 2009;27:5287–97.CrossRefPubMedPubMedCentral Roy R, Yang J, Moses MA. Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer. J Clin Oncol. 2009;27:5287–97.CrossRefPubMedPubMedCentral
17.
go back to reference Chu D, Zhang Z, Li Y, Zheng J, Dong G, Wang W, et al. Matrix metalloproteinase-9 is associated with disease-free survival and overall survival in patients with gastric cancer. Int J Cancer. 2011;129:887–95.CrossRefPubMed Chu D, Zhang Z, Li Y, Zheng J, Dong G, Wang W, et al. Matrix metalloproteinase-9 is associated with disease-free survival and overall survival in patients with gastric cancer. Int J Cancer. 2011;129:887–95.CrossRefPubMed
18.
go back to reference Cock-Rada AM, Medjkane S, Janski N, Yousfi N, Perichon M, Chaussepied M, et al. SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res. 2012;72:810–20.CrossRefPubMed Cock-Rada AM, Medjkane S, Janski N, Yousfi N, Perichon M, Chaussepied M, et al. SMYD3 promotes cancer invasion by epigenetic upregulation of the metalloproteinase MMP-9. Cancer Res. 2012;72:810–20.CrossRefPubMed
19.
go back to reference Jaskelioff M, Peterson CL. Chromatin and transcription: histones continue to make their marks. Nat Cell Biol. 2003;5:395–9.CrossRefPubMed Jaskelioff M, Peterson CL. Chromatin and transcription: histones continue to make their marks. Nat Cell Biol. 2003;5:395–9.CrossRefPubMed
20.
go back to reference Luo XG, Ding Y, Zhou QF, Ye L, Wang SZ, Xi T. SET and MYND domain containing protein 3 decreases sensitivity to dexamethasone and stimulates cell adhesion and migration in NIH3T3 cells. J Biosci Bioeng. 2007;103:444–50.CrossRefPubMed Luo XG, Ding Y, Zhou QF, Ye L, Wang SZ, Xi T. SET and MYND domain containing protein 3 decreases sensitivity to dexamethasone and stimulates cell adhesion and migration in NIH3T3 cells. J Biosci Bioeng. 2007;103:444–50.CrossRefPubMed
21.
go back to reference Kim H, Heo K, Kim JH, Kim K, Choi J, An W. Requirement of histone methyltransferase SMYD3 for estrogen receptor-mediated transcription. J Biol Chem. 2009;284:19867–77.CrossRefPubMedPubMedCentral Kim H, Heo K, Kim JH, Kim K, Choi J, An W. Requirement of histone methyltransferase SMYD3 for estrogen receptor-mediated transcription. J Biol Chem. 2009;284:19867–77.CrossRefPubMedPubMedCentral
22.
go back to reference Zou JN, Wang SZ, Yang JS, Luo XG, Xie JH, Xi T. Knockdown of SMYD3 by RNA interference down-regulates c-Met expression and inhibits cells migration and invasion induced by HGF. Cancer Lett. 2009;280:78–85.CrossRefPubMed Zou JN, Wang SZ, Yang JS, Luo XG, Xie JH, Xi T. Knockdown of SMYD3 by RNA interference down-regulates c-Met expression and inhibits cells migration and invasion induced by HGF. Cancer Lett. 2009;280:78–85.CrossRefPubMed
23.
go back to reference Zeng ZS, Huang Y, Cohen AM, Guillem JG. Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J Clin Oncol. 1996;14:3133–40.CrossRefPubMed Zeng ZS, Huang Y, Cohen AM, Guillem JG. Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J Clin Oncol. 1996;14:3133–40.CrossRefPubMed
24.
go back to reference Sampieri CL, de la Peña S, Ochoa-Lara M, Zenteno-Cuevas R, León-Córdoba K. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis. World J Gastroenterol. 2010;16:1500–5.CrossRefPubMedPubMedCentral Sampieri CL, de la Peña S, Ochoa-Lara M, Zenteno-Cuevas R, León-Córdoba K. Expression of matrix metalloproteinases 2 and 9 in human gastric cancer and superficial gastritis. World J Gastroenterol. 2010;16:1500–5.CrossRefPubMedPubMedCentral
25.
go back to reference Ruokolainen H, Pääkkö P, Turpeenniemi-Hujanen T. Expression of matrix metalloproteinase-9 in head and neck squamous cell carcinoma: a potential marker for prognosis. Clin Cancer Res. 2004;10:3110–6.CrossRefPubMed Ruokolainen H, Pääkkö P, Turpeenniemi-Hujanen T. Expression of matrix metalloproteinase-9 in head and neck squamous cell carcinoma: a potential marker for prognosis. Clin Cancer Res. 2004;10:3110–6.CrossRefPubMed
Metadata
Title
Overexpression of SMYD3 and matrix metalloproteinase-9 are associated with poor prognosis of patients with gastric cancer
Authors
Yong Liu
Honggen Liu
Xuegang Luo
Jingyu Deng
Yuan Pan
Han Liang
Publication date
01-06-2015
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 6/2015
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-015-3077-z

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