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
Oncology Reports
Join Editorial Board Propose a Special Issue
Print ISSN: 1021-335X Online ISSN: 1791-2431
Journal Cover
April 2013 Volume 29 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
April 2013 Volume 29 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

Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma

  • Authors:
    • Ningning Cong
    • Ping Du
    • Anling Zhang
    • Fajuan Shen
    • Juan Su
    • Peiyu Pu
    • Tao Wang
    • Jie Zjang
    • Chunsheng Kang
    • Qingyu Zhang
  • View Affiliations / Copyright

    Affiliations: Department of Gastroenterology, Tianjin Medical University General Hospital, Tianjin 300052, P.R. China, Department of Neurosurgery, Tianjin Medical University General Hospital and Laboratory of Neuro-Oncology, Tianjin Neurological Institute, Tianjin 300052, P.R. China
  • Pages: 1579-1587
    |
    Published online on: January 31, 2013
       https://doi.org/10.3892/or.2013.2267
  • 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

In a previous study, we found that microRNA (miRNA)-200a suppresses Wnt/β-catenin signaling by interacting with β-catenin, thereby inhibiting migration, invasion and proliferation. However, the mechanism involved in this suppression remains unclear. In the present study, we investigated the underlying mechanism of miR-200a regulation of epithelial-mesenchymal transition (EMT) in gastric carcinoma cells, and confirmed the tumor suppressor role of miR-200a in vivo. The expressions of miRNA-200a, -200b and -200c, identified by fluorescent in situ hybridization, were downregulated and inversely correlated with WHO grades of gastric adenocarcinoma (GA). The expression of the potential miR-200a target genes ZEB1 and ZEB2 was detected immunohistochemically. These examinations used the same tissue microarrays to analyze the relationships between miR-200a and potential target genes. The expression of miR-200a and ZEB1/ZEB2 in the same GA tissue microarrays was inversely related. Restored miR-200a expression inhibited tumor growth in nude mice harboring subcutaneous SGC7901 xenografts. The expression of N-cadherin, β-catenin, Twist1 and Snail2 decreased, and E-cadherin levels increased, when miR-200a was elevated, as tested by fluorescence microscopy and immunohistochemistry. Similar results were observed in vivo. We found upregulated miR-200a expression to increase E-cadherin and suppress the Wnt/β-catenin pathway by targeting ZEB1 and ZEB2 in GA, thus delaying tumor growth in vivo. The effect of miR-200a on Wnt/β-catenin signaling may provide a therapeutic target against EMT.
View Figures

Figure 1

Figure 2

Figure 3

Figure 4

Figure 5

View References

1 

Zhang X, Nie Y, Du Y, Cao J, Shen B and Li Y: MicroRNA-181a promotes gastric cancer by negatively regulating tumor suppressor KLF6. Tumour Biol. 33:1589–1597. 2012. View Article : Google Scholar : PubMed/NCBI

2 

Wang M, Li C, Nie H, et al: Down-regulated miR-625 suppresses invasion and metastasis of gastric cancer by targeting ILK. FEBS Lett. 586:2382–2388. 2012. View Article : Google Scholar : PubMed/NCBI

3 

Li Z, Cao Y, Jie Z, et al: miR-495 and miR-551a inhibit the migration and invasion of human gastric cancer cells by directly interacting with PRL-3. Cancer Lett. 323:41–47. 2012. View Article : Google Scholar : PubMed/NCBI

4 

Hua Y, Duan S, Murmann AE, et al: miRConnect: identifying effector genes of miRNAs and miRNA families in cancer cells. PLoS One. 6:e265212011. View Article : Google Scholar : PubMed/NCBI

5 

Bartel DP: MicroRNAs: target recognition and regulatory functions. Cell. 136:215–233. 2009. View Article : Google Scholar : PubMed/NCBI

6 

Kim VN, Han J and Siomi MC: Biogenesis of small RNAs in animals. Nat Rev Mol Cell Biol. 10:126–139. 2009. View Article : Google Scholar : PubMed/NCBI

7 

Schickel R, Boyerinas B, Park SM and Peter ME: MicroRNAs: key players in the immune system, differentiation, tumorigenesis and cell death. Oncogene. 27:5959–5974. 2008. View Article : Google Scholar : PubMed/NCBI

8 

Bartel DP: MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 116:281–297. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Negrini M, Nicoloso MS and Calin GA: MicroRNAs and cancer - new paradigms in molecular oncology. Curr Opin Cell Biol. 21:470–479. 2009. View Article : Google Scholar : PubMed/NCBI

10 

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

11 

Howe EN, Cochrane DR and Richer JK: Targets of miR-200c mediate suppression of cell motility and anoikis resistance. Breast Cancer Res. 13:R452011. View Article : Google Scholar : PubMed/NCBI

12 

Schliekelman MJ, Gibbons DL, Faca VM, et al: Targets of the tumor suppressor miR-200 in regulation of the epithelial-mesenchymal transition in cancer. Cancer Res. 71:7670–7682. 2011. View Article : Google Scholar : PubMed/NCBI

13 

Slabakova E, Pernicova Z, Slavickova E, Starsichova A, Kozubik A and Soucek K: TGF-beta1-induced EMT of non-transformed prostate hyperplasia cells is characterized by early induction of SNAI2/Slug. Prostate. 71:1332–1343. 2011.PubMed/NCBI

14 

Xu J, Lamouille S and Derynck R: TGF-beta-induced epithelial to mesenchymal transition. Cell Res. 19:156–172. 2009. View Article : Google Scholar : PubMed/NCBI

15 

Davalos V, Moutinho C, Villanueva A, et al: Dynamic epigenetic regulation of the microRNA-200 family mediates epithelial and mesenchymal transitions in human tumorigenesis. Oncogene. 31:2062–2074. 2011. View Article : Google Scholar : PubMed/NCBI

16 

Zhao F, Zhang Q, Kang C, et al: Suppression of matrix metalloproteinase-9 expression by RNA interference inhibits SGC7901 gastric adenocarcinoma cell growth and invasion in vitro and in vivo. Med Oncol. 27:774–784. 2010. View Article : Google Scholar : PubMed/NCBI

17 

Su J, Zhang A, Shi Z, et al: MicroRNA-200a suppresses the Wnt/β-catenin signaling pathway by interacting with β-catenin. Int J Oncol. 40:1162–1170. 2012.

18 

Gregory PA, Bert AG, Paterson EL, et al: 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

19 

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

20 

Burk U, Schubert J, Wellner U, et al: A reciprocal repression between ZEB1 and members of the miR-200 family promotes EMT and invasion in cancer cells. EMBO Rep. 9:582–589. 2008. View Article : Google Scholar : PubMed/NCBI

21 

Wiklund ED, Bramsen JB, Hulf T, et al: 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

22 

Barron N, Keenan J, Gammell P, et al: Biochemical relapses following radical prostatectomy and miR-200a levels in prostate cancer. Prostate. 7:1193–1199. 2011.PubMed/NCBI

23 

Guttilla IK, Adams BD and White BA: ERalpha, microRNAs, and the epithelial-mesenchymal transition in breast cancer. Trends Endocrinol Metab. 23:73–82. 2012. View Article : Google Scholar : PubMed/NCBI

24 

Roybal JD, Zang Y, Ahn YH, et al: miR-200 inhibits lung adenocarcinoma cell invasion and metastasis by targeting Flt1/VEGFR1. Mol Cancer Res. 9:25–35. 2011. View Article : Google Scholar : PubMed/NCBI

25 

Snowdon J, Zhang X, Childs T, Tron VA and Feilotter H: The microRNA-200 family is upregulated in endometrial carcinoma. PLoS One. 6:e228282011. View Article : Google Scholar : PubMed/NCBI

26 

Mateescu B, Batista L, Cardon M, et al: miR-141 and miR-200a act on ovarian tumorigenesis by controlling oxidative stress response. Nat Med. 17:1627–1635. 2011. View Article : Google Scholar : PubMed/NCBI

27 

Saydam O, Shen Y, Wurdinger T, et al: Downregulated microRNA-200a in meningiomas promotes tumor growth by reducing E-cadherin and activating the Wnt/beta-catenin signaling pathway. Mol Cell Biol. 29:5923–5940. 2009. View Article : Google Scholar : PubMed/NCBI

28 

Xia H, Ng SS, Jiang S, et al: miR-200a-mediated downregulation of ZEB2 and CTNNB1 differentially inhibits nasopharyngeal carcinoma cell growth, migration and invasion. Biochem Biophys Res Commun. 391:535–541. 2010. View Article : Google Scholar : PubMed/NCBI

29 

Han L, Yang Y, Yue X, et al: Inactivation of PI3K/AKT signaling inhibits glioma cell growth through modulation of beta-catenin-mediated transcription. Brain Res. 1366:9–17. 2010. View Article : Google Scholar : PubMed/NCBI

30 

Logan CY and Nusse R: The Wnt signaling pathway in development and disease. Annu Rev Cell Dev Biol. 20:781–810. 2004. View Article : Google Scholar : PubMed/NCBI

31 

Casas E, Kim J, Bendesky A, Ohno-Machado L, Wolfe CJ and Yang J: Snail2 is an essential mediator of Twist1-induced epithelial mesenchymal transition and metastasis. Cancer Res. 71:245–254. 2011. View Article : Google Scholar : PubMed/NCBI

32 

Ip YT, Park RE, Kosman D, Yazdanbakhsh K and Levine M: Dorsal-twist interactions establish snail expression in the presumptive mesoderm of the Drosophila embryo. Genes Dev. 6:1518–1530. 1992. View Article : Google Scholar : PubMed/NCBI

33 

Leptin M: Twist and snail as positive and negative regulators during Drosophila mesoderm development. Genes Dev. 5:1568–1576. 1991. View Article : Google Scholar : PubMed/NCBI

34 

Yang J, Mani SA, Donaher JL, et al: Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell. 117:927–939. 2004. View Article : Google Scholar : PubMed/NCBI

35 

Reinhold MI, Kapadia RM, Liao Z and Naski MC: The Wnt-inducible transcription factor Twist1 inhibits chondrogenesis. J Biol Chem. 281:1381–1388. 2006. View Article : Google Scholar : PubMed/NCBI

36 

Conacci-Sorrell M, Simcha I, Ben-Yedidia T, Blechman J, Savagner P and Ben-Ze’Ev A: Autoregulation of E-cadherin expression by cadherin-cadherin interactions: the roles of beta-catenin signaling, Slug, and MAPK. J Cell Biol. 163:847–857. 2003. View Article : Google Scholar : PubMed/NCBI

37 

Kurashige J, Kamohara H, Watanabe M, et al: MicroRNA-200b regulates cell proliferation, invasion, and migration by directly targeting ZEB2 in gastric carcinoma. Ann Surg Oncol. 19:656–664. 2012. View Article : Google Scholar : PubMed/NCBI

38 

Radisky DC: miR-200c at the nexus of epithelial-mesenchymal transition, resistance to apoptosis, and the breast cancer stem cell phenotype. Breast Cancer Res. 13:1102011. View Article : Google Scholar : PubMed/NCBI

Related Articles

  • Abstract
  • View
  • Download
  • Twitter
Copy and paste a formatted citation
Spandidos Publications style
Cong N, Du P, Zhang A, Shen F, Su J, Pu P, Wang T, Zjang J, Kang C, Zhang Q, Zhang Q, et al: Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma. Oncol Rep 29: 1579-1587, 2013.
APA
Cong, N., Du, P., Zhang, A., Shen, F., Su, J., Pu, P. ... Zhang, Q. (2013). Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma. Oncology Reports, 29, 1579-1587. https://doi.org/10.3892/or.2013.2267
MLA
Cong, N., Du, P., Zhang, A., Shen, F., Su, J., Pu, P., Wang, T., Zjang, J., Kang, C., Zhang, Q."Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma". Oncology Reports 29.4 (2013): 1579-1587.
Chicago
Cong, N., Du, P., Zhang, A., Shen, F., Su, J., Pu, P., Wang, T., Zjang, J., Kang, C., Zhang, Q."Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma". Oncology Reports 29, no. 4 (2013): 1579-1587. https://doi.org/10.3892/or.2013.2267
Copy and paste a formatted citation
x
Spandidos Publications style
Cong N, Du P, Zhang A, Shen F, Su J, Pu P, Wang T, Zjang J, Kang C, Zhang Q, Zhang Q, et al: Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma. Oncol Rep 29: 1579-1587, 2013.
APA
Cong, N., Du, P., Zhang, A., Shen, F., Su, J., Pu, P. ... Zhang, Q. (2013). Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma. Oncology Reports, 29, 1579-1587. https://doi.org/10.3892/or.2013.2267
MLA
Cong, N., Du, P., Zhang, A., Shen, F., Su, J., Pu, P., Wang, T., Zjang, J., Kang, C., Zhang, Q."Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma". Oncology Reports 29.4 (2013): 1579-1587.
Chicago
Cong, N., Du, P., Zhang, A., Shen, F., Su, J., Pu, P., Wang, T., Zjang, J., Kang, C., Zhang, Q."Downregulated microRNA-200a promotes EMT and tumor growth through the wnt/β-catenin pathway by targeting the E-cadherin repressors ZEB1/ZEB2 in gastric adenocarcinoma". Oncology Reports 29, no. 4 (2013): 1579-1587. https://doi.org/10.3892/or.2013.2267
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