Skip to main content

Advertisement

SpringerLink
Log in

miR-137 suppresses the invasion and procedure of EMT of human breast cancer cell line MCF-7 through targeting CtBP1

  • Research Article
  • Published:
Human Cell Aims and scope Submit manuscript

Abstract

Distant metastasis is the predominant site of gastric cancer recurrence and the most common cause of death. Recently, accumulating evidence has established that aberrant epithelial-mesenchymal transition activation plays a crucial role in the genesis, invasion, and metastasis of various cancers, including breast cancer. In this paper, we found that miR-137, which has been reported to function as a tumor suppressor in a variety of cancers, could significantly suppress the migration and invasion of MCF-7 cells, which might be correlated with its suppressive effects on the EMT procedure. Upon transfection, the epithelial marker, E-cadherin, was up-regulated, and the mesenchymal markers, N-cadherin and Vimentin, were suppressed. Moreover, we also found that carboxyl-terminal binding protein 1 (CtBP1) was a putative target gene of miR-137 in MCF-7 cells, and might be involved in the suppressive effects, which might provide novel diagnostic and therapeutic options for human breast cancer in the future.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. DeSantis C, Ma J, Bryan L, Jemal A. Breast cancer statistics, 2013. CA Cancer J Clin. 2014;64(1):52–62. doi:10.3322/caac.21203.

    Article  PubMed  Google Scholar 

  2. Gatza ML, Lucas JE, Barry WT, Kim JW, Wang Q, Crawford MD, et al. A pathway-based classification of human breast cancer. Proc Natl Acad Sci USA. 2010;107(15):6994–9. doi:10.1073/pnas.0912708107.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  3. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial–mesenchymal transitions in development and disease. Cell. 2009;139(5):871–90. doi:10.1016/j.cell.2009.11.007.

    Article  PubMed  CAS  Google Scholar 

  4. Kalluri R, Weinberg RA. The basics of epithelial-mesenchymal transition. J Clin Investig. 2009;119(6):1420–8. doi:10.1172/jci39104.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  5. Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res. 2006;66(17):8319–26. doi:10.1158/0008-5472.can-06-0410.

    Article  PubMed  CAS  Google Scholar 

  6. Klymkowsky MW, Savagner P. Epithelial–mesenchymal transition: a cancer researcher’s conceptual friend and foe. Am J Pathol. 2009;174(5):1588–93. doi:10.2353/ajpath.2009.080545.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. Montemayor-Garcia C, Hardin H, Guo Z, Larrain C, Buehler D, Asioli S, et al. The role of epithelial mesenchymal transition markers in thyroid carcinoma progression. Endocr Pathol. 2013;24(4):206–12. doi:10.1007/s12022-013-9272-9.

    Article  PubMed  CAS  Google Scholar 

  8. Liang Q, Li L, Zhang J, Lei Y, Wang L, Liu DX, et al. CDK5 is essential for TGF-beta1-induced epithelial-mesenchymal transition and breast cancer progression. Sci Rep. 2013;3:2932. doi:10.1038/srep02932.

    PubMed  PubMed Central  Google Scholar 

  9. Vincent-Salomon A, Thiery JP. Host microenvironment in breast cancer development: epithelial-mesenchymal transition in breast cancer development. Breast Cancer Res. 2003;5(2):101–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Hirohashi S. Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol. 1998;153(2):333–9. doi:10.1016/s0002-9440(10)65575-7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Garg M. Targeting microRNAs in epithelial-to-mesenchymal transition-induced cancer stem cells: therapeutic approaches in cancer. Expert Opin Ther Targets. 2015;19(2):285–97. doi:10.1517/14728222.2014.975794.

    Article  PubMed  CAS  Google Scholar 

  12. Balaguer F, Link A, Lozano JJ, Cuatrecasas M, Nagasaka T, Boland CR, et al. Epigenetic silencing of miR-137 is an early event in colorectal carcinogenesis. Cancer Res. 2010;70(16):6609–18. doi:10.1158/0008-5472.can-10-0622.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Chen X, Wang J, Shen H, Lu J, Li C, Hu DN, et al. Epigenetics, microRNAs, and carcinogenesis: functional role of microRNA-137 in uveal melanoma. Invest Ophthalmol Vis Sci. 2011;52(3):1193–9. doi:10.1167/iovs.10-5272.

    Article  PubMed  CAS  Google Scholar 

  14. Zhao Y, Li Y, Lou G, Zhao L, Xu Z, Zhang Y, et al. miR-137 targets estrogen-related receptor alpha and impairs the proliferative and migratory capacity of breast cancer cells. PLoS ONE. 2012;7(6):e39102. doi:10.1371/journal.pone.0039102.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  15. Zhu X, Li Y, Shen H, Li H, Long L, Hui L, et al. miR-137 restoration sensitizes multidrug-resistant MCF-7/ADM cells to anticancer agents by targeting YB-1. Acta Biochim Biophys Sin. 2013;45(2):80–6. doi:10.1093/abbs/gms099.

    Article  PubMed  CAS  Google Scholar 

  16. Chinnadurai G. The transcriptional corepressor CtBP: a foe of multiple tumor suppressors. Cancer Res. 2009;69(3):731–4. doi:10.1158/0008-5472.can-08-3349.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Deng Y, Deng H, Bi F, Liu J, Bemis LT, Norris D, et al. MicroRNA-137 targets carboxyl-terminal binding protein 1 in melanoma cell lines. Int J Biol Sci. 2011;7(1):133–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Thiery JP, Sleeman JP. Complex networks orchestrate epithelial-mesenchymal transitions. Nat Rev Mol Cell Biol. 2006;7(2):131–42. doi:10.1038/nrm1835.

    Article  PubMed  CAS  Google Scholar 

  19. Kong YW, Ferland-McCollough D, Jackson TJ, Bushell M. microRNAs in cancer management. Lancet Oncol. 2012;13(6):e249–58. doi:10.1016/s1470-2045(12)70073-6.

    Article  PubMed  CAS  Google Scholar 

  20. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116(2):281–97.

    Article  PubMed  CAS  Google Scholar 

  21. Chen K, Rajewsky N. The evolution of gene regulation by transcription factors and microRNAs. Nat Rev Genet. 2007;8(2):93–103. doi:10.1038/nrg1990.

    Article  PubMed  CAS  Google Scholar 

  22. Liu M, Lang N, Qiu M, Xu F, Li Q, Tang Q, et al. miR-137 targets Cdc42 expression, induces cell cycle G1 arrest and inhibits invasion in colorectal cancer cells. Int J Cancer. 2011;128(6):1269–79. doi:10.1002/ijc.25452.

    Article  PubMed  CAS  Google Scholar 

  23. Bi Y, Han Y, Bi H, Gao F, Wang X. miR-137 impairs the proliferative and migratory capacity of human non-small cell lung cancer cells by targeting paxillin. Hum Cell. 2014;27(3):95–102. doi:10.1007/s13577-013-0085-4.

    Article  PubMed  CAS  Google Scholar 

  24. Subramanian T, La Regina M, Chinnadurai G. Enhanced ras oncogene mediated cell transformation and tumorigenesis by adenovirus 2 mutants lacking the C-terminal region of E1a protein. Oncogene. 1989;4(4):415–20.

    PubMed  CAS  Google Scholar 

  25. Frisch SM. Antioncogenic effect of adenovirus E1A in human tumor cells. Proc Natl Acad Sci USA. 1991;88(20):9077–81.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Grooteclaes ML, Frisch SM. Evidence for a function of CtBP in epithelial gene regulation and anoikis. Oncogene. 2000;19(33):3823–8. doi:10.1038/sj.onc.1203721.

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

This research was supported through the Fundamental Research Funds for the National Natural Science Foundation of China (30972932, 81173601).

Author information

Author notes

    Authors and Affiliations

    1. Department of Breast and Thyroid Surgery, The Affiliated Hospital of Binzhou Medical University, Binzhou, 256603, Shandong Province, People’s Republic of China

      Yong Han, Guoqiang Zhang, Kai Cheng & Zhenlin Yang

    2. Department of Respiratory Medicine, The Affiliated Hospital of Binzhou Medical University, Binzhou, 256603, Shandong Province, People’s Republic of China

      Yueyang Bi

    3. Department of General Surgery, The Jingqu Hospital of Weihai City, Weihai, 264200, Shandong Province, People’s Republic of China

      Haiyang Bi

    4. Department of Gynecology and Obstetrics, The People’s Hospital of South District of Qingdao, Qingdao, 266000, Shandong Province, People’s Republic of China

      Caimei Diao

    Authors
    1. Yong Han
      View author publications

      You can also search for this author in PubMed Google Scholar

    2. Yueyang Bi
      View author publications

      You can also search for this author in PubMed Google Scholar

    3. Haiyang Bi
      View author publications

      You can also search for this author in PubMed Google Scholar

    4. Caimei Diao
      View author publications

      You can also search for this author in PubMed Google Scholar

    5. Guoqiang Zhang
      View author publications

      You can also search for this author in PubMed Google Scholar

    6. Kai Cheng
      View author publications

      You can also search for this author in PubMed Google Scholar

    7. Zhenlin Yang
      View author publications

      You can also search for this author in PubMed Google Scholar

    Corresponding author

    Correspondence to Zhenlin Yang.

    Ethics declarations

    Conflict of interest

    None declared.

    Additional information

    Y. Han and Y. Bi contributed equally to this work.

    Rights and permissions

    Reprints and permissions

    About this article

    Check for updates. Verify currency and authenticity via CrossMark

    Cite this article

    Han, Y., Bi, Y., Bi, H. et al. miR-137 suppresses the invasion and procedure of EMT of human breast cancer cell line MCF-7 through targeting CtBP1 . Human Cell 29, 30–36 (2016). https://doi.org/10.1007/s13577-015-0124-4

    Download citation

    • Received:

    • Accepted:

    • Published:

    • Issue Date:

    • DOI: https://doi.org/10.1007/s13577-015-0124-4

    Keywords

    Search

    Navigation