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
International Journal of Molecular Medicine
Join Editorial Board Propose a Special Issue
Print ISSN: 1107-3756 Online ISSN: 1791-244X
Journal Cover
2014-April Volume 33 Issue 4

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
2014-April Volume 33 Issue 4

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

Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma

  • Authors:
    • Shunji Tamagawa
    • Levent Bekir Beder
    • Muneki Hotomi
    • Mehmet Gunduz
    • Kazuya Yata
    • Reidar Grenman
    • Noboru Yamanaka
  • View Affiliations / Copyright

    Affiliations: Department of Otolaryngology - Head and Neck Surgery, Wakayama Medical University, Wakayama, Japan, Department of Otolaryngology, Turgut Ozal University, Faculty of Medicine, Ankara, Turkey, Department of Otorhinolaryngology - Head and Neck Surgery, Turku University Central Hospital, Turku, Finland
  • Pages: 879-886
    |
    Published online on: January 14, 2014
       https://doi.org/10.3892/ijmm.2014.1625
  • 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

Epithelial-mesenchymal-transition (EMT) is a critical step in tumor invasion and metastasis, while its fate is mainly defined by the balanced expression between the miR-200 family and ZEB transcription factors. In this study, we observed a reciprocal correlation between miR-200c/mir-141 and ZEB1, as well as between ZEB2 and E-cadherin expression in a panel of 13 head and neck squamous cell carcinoma (HNSCC) cell lines. We also confirmed that the enforced expression of miR-200c and miR-141 significantly reduced the migration capacity of HNSCC cells. Accordingly, the enforced expression of miR-200c and mir-141 resulted in a significant upregulation in E-cadherin expression, contrary to the significant downregulation in ZEB1 expression in 3 cell lines (UTSCC-24A, UTSCC-24B and UTSCC-6A cells). Another pair of cell lines, UTSCC-60A and UTSCC‑ 60B failed to show a significant change in the expression of E-cadherin or ZEB1/ZEB2 during the enforced expression of miR-200c/miR-141. To address the issue, we focused on the hypermethylation status of the ZEB1/2 promoters, which have both been shown to include wide CpG islands. We observed a marked upregulation in both ZEB1 and ZEB2 mRNA expression following treatment with a demethylating agent in both pairs of UTSCC cell lines. In conclusion, our findings confirm the existence of a reciprocal correlation between the mir-200 family and the ZEB family, and demonstrate the role of the miR-200 family in EMT, as well as in the migration and invasion ability of HNSCC cells. Furthermore, our data suggest that the promoter hypermethylation of ZEB1 and ZEB2 may play an essential role and may overshadow the effects of the miR-200 family in the regulation of EMT during carcinogenesis.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Tsuji T, Ibaragi S and Hu GF: Epithelial-mesenchymal transition and cell cooperativity in metastasis. Cancer Res. 69:7135–7139. 2009. View Article : Google Scholar : PubMed/NCBI

2 

Hill L, Browne G and Tulchinsky E: ZEB/miR-200 feedback loop: At the crossroads of signal transduction in cancer. Int J Cancer. 132:745–754. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Tran N, McLean T, Zhang X, Zhao CJ, Thomson JM, O’Brien C and Rose B: MicroRNA expression profiles in head and neck cancer cell lines. Biochem Biophys Res Commun. 358:12–17. 2007. View Article : Google Scholar

4 

Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, Vadas MA, Khew-Goodall Y and Goodall GJ: The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 10:593–601. 2008. View Article : Google Scholar : PubMed/NCBI

5 

Park SM, Gaur AB, Lengyel E and Peter ME: The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 22:894–907. 2008. View Article : Google Scholar : PubMed/NCBI

6 

Brabletz S and Brabletz T: The ZEB/miR-200 feedback loop - a motor of cellular plasticity in development and cancer? EMBO Rep. 11:670–677. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI

8 

Beder LB, Gunduz M, Hotomi M, Fujihara K, Shimada J, Tamura S, Gunduz E, Fukushima K, Yaykasli K, Grenman R, Shimizu K and Yamanaka N: T-lymphocyte maturation-associated protein gene as a candidate metastasis suppressor for head and neck squamous cell carcinomas. Cancer Sci. 100:873–880. 2009. View Article : Google Scholar : PubMed/NCBI

9 

Griffiths-Jones S, Grocock RJ, van Dongen S, Bateman A and Enright AJ: miRBase: microRNA sequences, targets and gene nomenclature. Nucleic Acids Res. 1:D140–D144. 2006. View Article : Google Scholar : PubMed/NCBI

10 

Vrba L, Jensen TJ, Garbe JC, Heimark RL, Cress AE, Dickinson S, Stampfer MR and Futscher BW: Role for DNA methylation in the regulation of miR-200c and miR-141 expression in normal and cancer cells. PLoS One. 5:e86972010. View Article : Google Scholar : PubMed/NCBI

11 

Wiklund ED, Bramsen JB, Hulf T, Dyrskjøt L, Ramanathan R, Hansen TB, Villadsen SB, Gao S, Ostenfeld MS, Borre M, Peter ME, Ørntoft TF, Kjems J and Clark SJ: Coordinated epigenetic repression of the miR-200 family and miR-205 in invasive bladder cancer. Int J Cancer. 128:1327–1334. 2011. View Article : Google Scholar : PubMed/NCBI

12 

Lim YY, Wright JA, Attema JL, Gregory PA, Bert AG, Smith E, Thomas D, Lopez AF, Drew PA, Khew-Goodall Y and Goodall GJ: Epigenetic modulation of the miR-200 family is associated with transition to a breast cancer stem-cell-like state. J Cell Sci. 126:2256–2266. 2013. View Article : Google Scholar : PubMed/NCBI

13 

Li A, Omura N, Hong SM, Vincent A, Walter K, Griffith M, Borges M and Goggins M: Pancreatic cancers epigenetically silence SIP1 and hypomethylate and overexpress miR-200a/200b in association with elevated circulating miR-200a and miR-200b levels. Cancer Res. 70:5226–5237. 2010. View Article : Google Scholar : PubMed/NCBI

14 

Rodenhiser DI, Andrews J, Kennette W, Sadikovic B, Mendlowitz A, Tuck AB and Chambers AF: Epigenetic mapping and functional analysis in a breast cancer metastasis model using whole-genome promoter tiling microarrays. Breast Cancer Res. 10:R622008. View Article : Google Scholar : PubMed/NCBI

15 

Acun T, Oztas E, Yagci T and Yakicier MC: SIP1 is downregulated in hepatocellular carcinoma by promoter hypermethylation. BMC Cancer. 11:2232011. View Article : Google Scholar : PubMed/NCBI

16 

Hidaka T, Nakahata S, Hatakeyama K, Hamasaki M, Yamashita K, Kohno T, Arai Y, Taki T, Nishida K, Okayama A, Asada Y, Yamaguchi R, Tsubouchi H, Yokota J, Taniwaki M, Higashi Y and Morishita K: Down-regulation of TCF8 is involved in the leukemogenesis of adult T-cell leukemia/lymphoma. Blood. 112:383–393. 2008. View Article : Google Scholar : PubMed/NCBI

17 

Su Z, Xia J and Zhao Z: Functional complementation between transcriptional methylation regulation and post-transcriptional microRNA regulation in the human genome. BMC Genomics. 12(Suppl 5): S152011. View Article : Google Scholar

18 

Wiklund ED, Gao S, Hulf T, Sibbritt T, Nair S, Costea DE, Villadsen SB, Bakholdt V, Bramsen JB, S⊘rensen JA, Krogdahl A, Clark SJ and Kjems J: MicroRNA alterations and associated aberrant DNA methylation patterns across multiple sample types in oral squamous cell carcinoma. PLoS One. 6:e278402011. View Article : Google Scholar : PubMed/NCBI

19 

Lo WL, Yu CC, Chiou GY, Chen YW, Huang PI, Chien CS, Tseng LM, Chu PY, Lu KH, Chang KW, Kao SY and Chiou SH: MicroRNA-200c attenuates tumour growth and metastasis of presumptive head and neck squamous cell carcinoma stem cells. J Pathol. 223:482–495. 2011. View Article : Google Scholar : PubMed/NCBI

20 

Korpal M, Ell BJ, Buffa FM, Ibrahim T, Blanco MA, Celià-Terrassa T, Mercatali L, Khan Z, Goodarzi H, Hua Y, Wei Y, Hu G, Garcia BA, Ragoussis J, Amadori D, Harris AL and Kang Y: Direct targeting of Sec23a by miR-200s influences cancer cell secretome and promotes metastatic colonization. Nat Med. 17:1101–1108. 2011. View Article : Google Scholar : PubMed/NCBI

21 

Korpal M, Lee ES, Hu G and Kang Y: The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 283:14910–14914. 2008. View Article : Google Scholar : PubMed/NCBI

22 

Zidar N, Bostjancic E, Gale N, Kojc N, Poljak M, Glavac D and Cardesa A: Down-regulation of microRNAs of the miR-200 family and miR-205, and an altered expression of classic and desmosomal cadherins in spindle cell carcinoma of the head and neck - hallmark of epithelial-mesenchymal transition. Hum Pathol. 42:482–488. 2011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Tamagawa S, Beder LB, Hotomi M, Gunduz M, Yata K, Grenman R and Yamanaka N: Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma. Int J Mol Med 33: 879-886, 2014.
APA
Tamagawa, S., Beder, L.B., Hotomi, M., Gunduz, M., Yata, K., Grenman, R., & Yamanaka, N. (2014). Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma. International Journal of Molecular Medicine, 33, 879-886. https://doi.org/10.3892/ijmm.2014.1625
MLA
Tamagawa, S., Beder, L. B., Hotomi, M., Gunduz, M., Yata, K., Grenman, R., Yamanaka, N."Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma". International Journal of Molecular Medicine 33.4 (2014): 879-886.
Chicago
Tamagawa, S., Beder, L. B., Hotomi, M., Gunduz, M., Yata, K., Grenman, R., Yamanaka, N."Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma". International Journal of Molecular Medicine 33, no. 4 (2014): 879-886. https://doi.org/10.3892/ijmm.2014.1625
Copy and paste a formatted citation
x
Spandidos Publications style
Tamagawa S, Beder LB, Hotomi M, Gunduz M, Yata K, Grenman R and Yamanaka N: Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma. Int J Mol Med 33: 879-886, 2014.
APA
Tamagawa, S., Beder, L.B., Hotomi, M., Gunduz, M., Yata, K., Grenman, R., & Yamanaka, N. (2014). Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma. International Journal of Molecular Medicine, 33, 879-886. https://doi.org/10.3892/ijmm.2014.1625
MLA
Tamagawa, S., Beder, L. B., Hotomi, M., Gunduz, M., Yata, K., Grenman, R., Yamanaka, N."Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma". International Journal of Molecular Medicine 33.4 (2014): 879-886.
Chicago
Tamagawa, S., Beder, L. B., Hotomi, M., Gunduz, M., Yata, K., Grenman, R., Yamanaka, N."Role of miR-200c/miR-141 in the regulation of epithelial-mesenchymal transition and migration in head and neck squamous cell carcinoma". International Journal of Molecular Medicine 33, no. 4 (2014): 879-886. https://doi.org/10.3892/ijmm.2014.1625
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