Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Oncology Letters
      • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Biomedical Reports
      • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • Information for Authors
    • Information for Reviewers
    • Information for Librarians
    • Information for Advertisers
    • Conferences
  • Language Editing
Spandidos Publications Logo
  • About
    • About Spandidos
    • Aims and Scopes
    • Abstracting and Indexing
    • Editorial Policies
    • Reprints and Permissions
    • Job Opportunities
    • Terms and Conditions
    • Contact
  • Journals
    • All Journals
    • Biomedical Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Experimental and Therapeutic Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Epigenetics
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Functional Nutrition
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Molecular Medicine
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • International Journal of Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Medicine International
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular and Clinical Oncology
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Molecular Medicine Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Letters
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • Oncology Reports
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
    • World Academy of Sciences Journal
      • Information for Authors
      • Editorial Policies
      • Editorial Board
      • Aims and Scope
      • Abstracting and Indexing
      • Bibliographic Information
      • Archive
  • Articles
  • Information
    • For Authors
    • For Reviewers
    • For Librarians
    • For Advertisers
    • Conferences
  • Language Editing
Login Register Submit
  • This site uses cookies
  • You can change your cookie settings at any time by following the instructions in our Cookie Policy. To find out more, you may read our Privacy Policy.

    I agree
Search articles by DOI, keyword, author or affiliation
Search
Advanced Search
presentation
Molecular Medicine Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1791-2997 Online ISSN: 1791-3004
Journal Cover
June-2014 Volume 9 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

Journals

International Journal of Molecular Medicine

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

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

Molecular Medicine Reports

Molecular Medicine Reports

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

Oncology Reports

Oncology Reports

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

Experimental and Therapeutic Medicine

Experimental and Therapeutic Medicine

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

Oncology Letters

Oncology Letters

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

Biomedical Reports

Biomedical Reports

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

Molecular and Clinical Oncology

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

World Academy of Sciences Journal

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

International Journal of Functional Nutrition

International Journal of Functional Nutrition

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

International Journal of Epigenetics

International Journal of Epigenetics

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

Medicine International

Medicine International

An International Open Access Journal Devoted to General Medicine.

Journal Cover
June-2014 Volume 9 Issue 6

Full Size Image

Sign up for eToc alerts
Recommend to Library

  • Article
  • Citations
    • Cite This Article
    • Download Citation
    • Create Citation Alert
    • Remove Citation Alert
    • Cited By
  • Similar Articles
    • Related Articles (in Spandidos Publications)
    • Similar Articles (Google Scholar)
    • Similar Articles (PubMed)
  • Download PDF
  • Download XML
  • View XML
Article

Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer

  • Authors:
    • Xin-Jiang Zhu
    • Jian Liu
    • Xiao-Yang Xu
    • Chun-Dong Zhang
    • Dong-Qiu Dai
  • View Affiliations / Copyright

    Affiliations: Department of Gastrointestinal Surgery, The Fourth Affiliated Hospital, China Medical University, Shenyang, Liaoning 110032, P.R. China
  • Pages: 2283-2292
    |
    Published online on: April 9, 2014
       https://doi.org/10.3892/mmr.2014.2135
  • Expand metrics +
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Metrics: Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )
Cited By (CrossRef): 0 citations Loading Articles...

This article is mentioned in:



Abstract

The present study aimed to investigate the role of histone modification and DNA methylation in epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 (EFEMP1) silencing in gastric cancer (GC). In the present study, four GC cell lines, and 45 paired normal and GC tissue samples were used to assess EFEMP1 expression using quantitative polymerase chain reaction (PCR), and EFEMP1 gene methylation status was evaluated by methylation‑specific PCR. The involvement of histone modification in GC cell lines was examined by a chromatin immunoprecipitation (ChIP) assay. The results demonstrated that EFEMP1 mRNA level and methylation status in the EFEMP1 promoter region was associated with tumor differentiation, depth of tumor invasion and lymph node metastasis. DNA methyltransferase inhibitor 5‑aza‑2'‑deoxycytidine (DAC) rapidly reduced DNA methylation and histone H3‑K9 trimethylation at the silenced loci and reactivated EFEMP1 expression. By contrast, the histone deacetylase inhibitor trichostatin A markedly increased histone H3‑K9 acetylation. However, it had no effect on DNA methylation, histone H3‑K9 trimethylation or gene expression. In conclusion, the results suggested that EFEMP1 may function as a tumor suppressor in GC. Aberrant DNA methylation and histone H3‑K9 trimethylation of EFEMP1 may be responsible for its downregulation in GC, and thus have an important role in tumor invasion and metastasis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Jemal A, Bray F, Center MM, et al: Global cancer statistics. CA Cancer J Clin. 61:69–90. 2011. View Article : Google Scholar

2 

Allis CD, Berger SL, Cote J, et al: New nomenclature for chromatin-modifying enzymes. Cell. 131:633–636. 2007. View Article : Google Scholar : PubMed/NCBI

3 

Cantone I and Fisher AG: Epigenetic programming and reprogramming during development. Nat Struct Mol Biol. 20:282–289. 2013. View Article : Google Scholar : PubMed/NCBI

4 

Albig AR, Neil JR and Schiemann WP: Fibulins 3 and 5 antagonize tumor angiogenesis in vivo. Cancer Res. 66:2621–2629. 2006. View Article : Google Scholar : PubMed/NCBI

5 

Yue W, Dacic S, Sun Q, et al: Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation. Clin Cancer Res. 13:4336–4344. 2007. View Article : Google Scholar : PubMed/NCBI

6 

Nomoto S, Kanda M, Okamura Y, et al: Epidermal growth factor-containing fibulin-like extracellular matrix protein 1, EFEMP1, a novel tumor suppressor gene detected in hepatocellular carcinoma using double combination array analysis. Ann Surg Oncol. 17:923–932. 2010. View Article : Google Scholar

7 

Kim YJ, Yoon HY, Kim SK, et al: EFEMP1 as a novel DNA methylation marker for prostate cancer: array-based DNA methylation and expression profiling. Clin Cancer Res. 17:4523–4530. 2011. View Article : Google Scholar : PubMed/NCBI

8 

Sadr-Nabavi A, Ramser J, Volkmann J, et al: Decreased expression of angiogenesis antagonist EFEMP1 in sporadic breast cancer is caused by aberrant promoter methylation and points to an impact of EFEMP1 as molecular biomarker. Int J Cancer. 124:1727–1735. 2009. View Article : Google Scholar

9 

Hwang CF, Chien CY, Huang SC, et al: Fibulin-3 is associated with tumour progression and a poor prognosis in nasopharyngeal carcinomas and inhibits cell migration and invasion via suppressed AKT activity. J Pathol. 222:367–379. 2010. View Article : Google Scholar : PubMed/NCBI

10 

En-lin S, Sheng-guo C and Hua-qiao W: The expression of EFEMP1 in cervical carcinoma and its relationship with prognosis. Gynecol Oncol. 117:417–422. 2010. View Article : Google Scholar : PubMed/NCBI

11 

Davidson B, Stavnes HT, Holth A, Chen X, Yang Y, et al: Gene expression signatures differentiate ovarian/peritoneal serous carcinoma from breast carcinoma in effusions. J Cell Mol Med. 15:535–544. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Seeliger H, Camaj P, Ischenko I, et al: EFEMP1 expression promotes in vivo tumor growth in human pancreatic adenocarcinoma. Mol Cancer Res. 7:189–198. 2009. View Article : Google Scholar : PubMed/NCBI

13 

Fahrner JA, Eguchi S, Herman JG and Baylin SB: Dependence of histone modifications and gene expression on DNA hypermethylation in cancer. Cancer Res. 62:7213–7218. 2002.PubMed/NCBI

14 

Cameron EE, Bachman KE, Myöhänen S, Herman JG and Baylin SB: Synergy of demethylation and histone deacetylase inhibition in the re-expression of genes silenced in cancer. Nat Genet. 21:103–107. 1999. View Article : Google Scholar : PubMed/NCBI

15 

Kuo MH and Allis CD: In vivo cross-linking and immunoprecipitation for studying dynamic Protein:DNA associations in a chromatin environment. Methods. 19:425–433. 1999. View Article : Google Scholar : PubMed/NCBI

16 

Wang R, Zhang YW and Chen LB: Aberrant promoter methylation of FBLN-3 gene and clinicopathological significance in non-small cell lung carcinoma. Lung Cancer. 69:239–244. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Sharma S, Kelly TK and Jones PA: Epigenetics in cancer. Carcinogenesis. 31:27–36. 2010. View Article : Google Scholar

18 

Meng CF, Zhu XJ, Peng G and Dai DQ: Role of histone modifications and DNA methylation in the regulation of O6-methylguanine-DNA methyltransferase gene expression in human stomach cancer cells. Cancer Invest. 28:331–339. 2010. View Article : Google Scholar : PubMed/NCBI

19 

Meng CF, Zhu XJ, Peng G and Dai DQ: Promoter histone H3 lysine 9 di-methylation is associated with DNA methylation and aberrant expression of p16 in gastric cancer cells. Oncol Rep. 22:1221–1227. 2009.PubMed/NCBI

20 

Chang X, Zhang S, Ma J, et al: Association of NDRG1 gene promoter methylation with reduced NDRG1 expression in gastric cancer cells and tissue specimens. Cell Biochem Biophys. 66:93–101. 2013. View Article : Google Scholar : PubMed/NCBI

21 

Grewal SI and Moazed D: Heterochromatin and epigenetic control of gene expression. Science. 301:798–802. 2003. View Article : Google Scholar : PubMed/NCBI

22 

Peters AH, Mermoud JE, O’Carroll D, et al: Histone H3 lysine 9 methylation is an epigenetic imprint of facultative heterochromatin. Nat Genet. 30:77–80. 2002. View Article : Google Scholar : PubMed/NCBI

23 

Zhang Y and Marmorstein LY: Focus on molecules: fibulin-3 (EFEMP1). Exp Eye Res. 90:374–375. 2010. View Article : Google Scholar : PubMed/NCBI

24 

Hu Y, Pioli PD, Siegel E, et al: EFEMP1 suppresses malignant glioma growth and exerts its action within the tumor extracellular compartment. Mol Cancer. 10:1232011. View Article : Google Scholar : PubMed/NCBI

25 

Kim EJ, Lee SY, Woo MK, et al: Fibulin-3 promoter methylation alters the invasive behavior of non-small cell lung cancer cell lines via MMP-7 and MMP-2 regulation. Int J Oncol. 40:402–408. 2012.PubMed/NCBI

26 

Tong JD, Jiao NL, Wang YX, Zhang YW and Han F: Downregulation of fibulin-3 gene by promoter methylation in colorectal cancer predicts adverse prognosis. Neoplasma. 58:441–448. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Yang T, Qiu H, Bao W, et al: Epigenetic inactivation of EFEMP1 is associated with tumor suppressive function in endometrial carcinoma. PLoS One. 8:e674582013. View Article : Google Scholar : PubMed/NCBI

28 

Jaenisch R and Bird A: Epigenetic regulation of gene expression: how the genome integrates intrinsic and environmental signals. Nat Genet. 33(Suppl): 245–254. 2003. View Article : Google Scholar : PubMed/NCBI

29 

Nawrocki ST, Carew JS, Douglas L, et al: Histone deacetylase inhibitors enhance lexatumumab-induced apoptosis via a p21Cip1-dependent decrease in survivin levels. Cancer Res. 67:6987–6994. 2007. View Article : Google Scholar : PubMed/NCBI

30 

Chang X, Li Z, Ma J, et al: DNA methylation of NDRG2 in gastric cancer and its clinical significance. Dig Dis Sci. 58:715–723. 2013. View Article : Google Scholar : PubMed/NCBI

31 

Zhi Y, Chen J, Zhang S, et al: Down-regulation of CXCL12 by DNA hypermethylation and its involvement in gastric cancer metastatic progression. Dig Dis Sci. 57:650–659. 2012. View Article : Google Scholar : PubMed/NCBI

32 

Fuks F, Hurd PJ, Deplus R and Kouzarides T: The DNA methyltransferases associate with HP1 and the SUV39H1 histone methyltransferase. Nucleic Acids Res. 31:2305–2312. 2003. View Article : Google Scholar : PubMed/NCBI

33 

Wozniak RJ, Klimecki WT, Lau SS, Feinstein Y and Futscher BW: 5-Aza-2′-deoxycytidine-mediated reductions in G9A histone methyltransferase and histone H3 K9 di-methylation levels are linked to tumor suppressor gene reactivation. Oncogene. 26:77–90. 2007.

34 

Lin W and Dent SY: Functions of histone-modifying enzymes in development. Curr Opin Genet Dev. 16:137–142. 2006. View Article : Google Scholar

35 

Martin C and Zhang Y: The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol. 6:838–849. 2005. View Article : Google Scholar : PubMed/NCBI

36 

Hu Q, Yu L, Chen R, et al: 5-aza-2′-deoxycytidine improves the sensitivity of endometrial cancer cells to progesterone therapy. Int J Gynecol Cancer. 22:951–959. 2012.

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Zhu X, Liu J, Xu X, Zhang C and Dai D: Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer. Mol Med Rep 9: 2283-2292, 2014.
APA
Zhu, X., Liu, J., Xu, X., Zhang, C., & Dai, D. (2014). Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer. Molecular Medicine Reports, 9, 2283-2292. https://doi.org/10.3892/mmr.2014.2135
MLA
Zhu, X., Liu, J., Xu, X., Zhang, C., Dai, D."Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer". Molecular Medicine Reports 9.6 (2014): 2283-2292.
Chicago
Zhu, X., Liu, J., Xu, X., Zhang, C., Dai, D."Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer". Molecular Medicine Reports 9, no. 6 (2014): 2283-2292. https://doi.org/10.3892/mmr.2014.2135
Copy and paste a formatted citation
x
Spandidos Publications style
Zhu X, Liu J, Xu X, Zhang C and Dai D: Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer. Mol Med Rep 9: 2283-2292, 2014.
APA
Zhu, X., Liu, J., Xu, X., Zhang, C., & Dai, D. (2014). Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer. Molecular Medicine Reports, 9, 2283-2292. https://doi.org/10.3892/mmr.2014.2135
MLA
Zhu, X., Liu, J., Xu, X., Zhang, C., Dai, D."Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer". Molecular Medicine Reports 9.6 (2014): 2283-2292.
Chicago
Zhu, X., Liu, J., Xu, X., Zhang, C., Dai, D."Novel tumor-suppressor gene epidermal growth factor‑containing fibulin‑like extracellular matrix protein 1 is epigenetically silenced and associated with invasion and metastasis in human gastric cancer". Molecular Medicine Reports 9, no. 6 (2014): 2283-2292. https://doi.org/10.3892/mmr.2014.2135
Follow us
  • Twitter
  • LinkedIn
  • Facebook
About
  • Spandidos Publications
  • Careers
  • Cookie Policy
  • Privacy Policy
How can we help?
  • Help
  • Live Chat
  • Contact
  • Email to our Support Team