Log in

microRNA-137 is downregulated in thyroid cancer and inhibits proliferation and invasion by targeting EGFR

  • Original Article
  • Published:
Tumor Biology

Abstract

microRNA-137 expression is downregulated in several tumors. To date, its expression and function in human thyroid cancer remain unexplored. The aim of this study is to identify its expression, function, and molecular mechanism in thyroid cancer. microRNA-137 (miR-137) downregulation was observed in thyroid cancer tissues compared with normal thyroid tissues. miR-137 mimics downregulated B-CPAP cell proliferation, colony formation ability, and invasion, with suppressed expression of cyclin E, MMP2, p-ERK, and p-AKT. miR-137 inhibitor transfection in TPC-1 cell line showed the opposite effects. With prediction software and luciferase reporter assay, we found that epidermal growth factor receptor (EGFR) was a target of miR-137. Transfection of miR-137 mimic suppressed EGFR protein and messenger RNA (mRNA) expression. EGFR small interfering RNA (siRNA) abrogated the role of miR-137 inhibitor on cyclin E, MMP2, p-ERK, and p-AKT. In addition, we found a negative correlation of EGFR and miR-137 in thyroid cancer tissues. In conclusion, the present study showed that miR-137 downregulation is associated with malignant progression of thyroid cancer. miR-137 inhibits growth and invasion by targeting EGFR in thyroid cancer cells.

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

Access this article

Subscribe and save

Springer+ Basic
EUR 32.99 /Month
  • Get 10 units per month
  • Download Article/Chapter or Ebook
  • 1 Unit = 1 Article or 1 Chapter
  • Cancel anytime
Subscribe now

Buy Now

Price includes VAT (Germany)

Instant access to the full article PDF.

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  1. Siegel R et al. Cancer statistics, 2014. CA Cancer J Clin. 2014;64(1):9–29.

    Article  PubMed  Google Scholar 

  2. Griffith OL et al. Biomarker panel diagnosis of thyroid cancer: a critical review. Expert Rev Anticancer Ther. 2008;8(9):1399–413.

    Article  CAS  PubMed  Google Scholar 

  3. Sipos JA, Mazzaferri EL. Thyroid cancer epidemiology and prognostic variables. Clin Oncol (R Coll Radiol). 2010;22(6):395–404.

    Article  CAS  Google Scholar 

  4. Lu J et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.

    Article  CAS  PubMed  Google Scholar 

  5. Yanaihara N et al. Unique microRNA molecular profiles in lung cancer diagnosis and prognosis. Cancer Cell. 2006;9(3):189–98.

    Article  CAS  PubMed  Google Scholar 

  6. Takamizawa J et al. Reduced expression of the let-7 microRNAs in human lung cancers in association with shortened postoperative survival. Cancer Res. 2004;64(11):3753–6.

    Article  CAS  PubMed  Google Scholar 

  7. Visone R et al. Specific microRNAs are downregulated in human thyroid anaplastic carcinomas. Oncogene. 2007;26(54):7590–5.

    Article  CAS  PubMed  Google Scholar 

  8. Zhao S, Li J. Sphingosine-1-phosphate induces the migration of thyroid follicular carcinoma cells through the microRNA-17/PTK6/ERK1/2 pathway. PLoS One. 2015;10(3):e0119148.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Dettmer M et al. Comprehensive microRNA expression profiling identifies novel markers in follicular variant of papillary thyroid carcinoma. Thyroid. 2013;23(11):1383–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Weber F et al. A limited set of human microRNA is deregulated in follicular thyroid carcinoma. J Clin Endocrinol Metab. 2006;91(9):3584–91.

    Article  CAS  PubMed  Google Scholar 

  11. Han Y et al. miR-137 suppresses the invasion and procedure of EMT of human breast cancer cell line MCF-7 through targeting CtBP1. Hum Cell. 2015.

  12. Kang N et al. Silencing of miR-137 by aberrant promoter hypermethylation in surgically resected lung cancer. Lung Cancer. 2015;89(2):99–103.

    Article  PubMed  Google Scholar 

  13. Guo J et al. miR-137 suppresses cell growth in ovarian cancer by targeting AEG-1. Biochem Biophys Res Commun. 2013;441(2):357–63.

    Article  CAS  PubMed  Google Scholar 

  14. Zhu X et al. miR-137 inhibits the proliferation of lung cancer cells by targeting Cdc42 and Cdk6. FEBS Lett. 2013;587(1):73–81.

    Article  CAS  PubMed  Google Scholar 

  15. Chen Q et al. miR-137 is frequently down-regulated in gastric cancer and is a negative regulator of Cdc42. Dig Dis Sci. 2011;56(7):2009–16.

    Article  CAS  PubMed  Google Scholar 

  16. Liu M 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.

    Article  CAS  PubMed  Google Scholar 

  17. Hao S et al. miR-137 inhibits proliferation of melanoma cells by targeting PAK2. Exp Dermatol. 2015.

  18. Sun Y et al. miR-124, miR-137 and miR-340 regulate colorectal cancer growth via inhibition of the Warburg effect. Oncol Rep. 2012;28(4):1346–52.

    CAS  PubMed  Google Scholar 

  19. Althoff K et al. MiR-137 functions as a tumor suppressor in neuroblastoma by downregulating KDM1A. Int J Cancer. 2013;133(5):1064–73.

    Article  CAS  PubMed  Google Scholar 

  20. Sun G et al. Overexpressed miRNA-137 inhibits human glioma cells growth by targeting Rac1. Cancer Biother Radiopharm. 2013;28(4):327–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Bi Y et al. 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.

    Article  CAS  PubMed  Google Scholar 

  22. Liu LL et al. FoxD3-regulated microRNA-137 suppresses tumour growth and metastasis in human hepatocellular carcinoma by targeting AKT2. Oncotarget. 2014;5(13):5113–24.

    Article  PubMed  PubMed Central  Google Scholar 

  23. Steponaitiene R et al. Epigenetic silencing of miR-137 is a frequent event in gastric carcinogenesis. Mol Carcinog. 2015.

  24. Zheng X et al. MicroRNA library-based functional screening identified miR-137 as a suppresser of gastric cancer cell proliferation. J Cancer Res Clin Oncol. 2015;141(5):785–95.

    Article  CAS  PubMed  Google Scholar 

  25. Lee JM et al. A contrasting function for miR-137 in embryonic mammogenesis and adult breast carcinogenesis. Oncotarget. 2015;6(26):22048–59.

    Article  PubMed  PubMed Central  Google Scholar 

  26. **u Y et al. MicroRNA-137 upregulation increases bladder cancer cell proliferation and invasion by targeting PAQR3. PLoS One. 2014;9(10):e109734.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Liang W et al. Down-regulation of SOSTDC1 promotes thyroid cancer cell proliferation via regulating cyclin A2 and cyclin E2. Oncotarget. 2015.

  28. Kalhori V, Tornquist K. MMP2 and MMP9 participate in S1P-induced invasion of follicular ML-1 thyroid cancer cells. Mol Cell Endocrinol. 2015;404:113–22.

    Article  CAS  PubMed  Google Scholar 

  29. Tian X et al. Relationship between protein expression of VEGF-C, MMP-2 and lymph node metastasis in papillary thyroid cancer. J Int Med Res. 2008;36(4):699–703.

    Article  CAS  PubMed  Google Scholar 

  30. Dong QZ et al. Derlin-1 is overexpressed in non-small cell lung cancer and promotes cancer cell invasion via EGFR-ERK-mediated up-regulation of MMP-2 and MMP-9. Am J Pathol. 2013;182(3):954–64.

    Article  CAS  PubMed  Google Scholar 

  31. Kharman-Biz A et al. Expression of activator protein-1 (AP-1) family members in breast cancer. BMC Cancer. 2013;13:441.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Cheng SP et al. Leptin enhances migration of human papillary thyroid cancer cells through the PI3K/AKT and MEK/ERK signaling pathways. Oncol Rep. 2011;26(5):1265–71.

    CAS  PubMed  Google Scholar 

  33. Gule MK et al. Targeted therapy of VEGFR2 and EGFR significantly inhibits growth of anaplastic thyroid cancer in an orthotopic murine model. Clin Cancer Res. 2011;17(8):2281–91.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rebai M et al. Association of EGFR and HER2 polymorphisms with risk and clinical features of thyroid cancer. Genet Test Mol Biomarkers. 2009;13(6):779–84.

    Article  CAS  PubMed  Google Scholar 

  35. Schiff BA et al. Epidermal growth factor receptor (EGFR) is overexpressed in anaplastic thyroid cancer, and the EGFR inhibitor gefitinib inhibits the growth of anaplastic thyroid cancer. Clin Cancer Res. 2004;10(24):8594–602.

    Article  CAS  PubMed  Google Scholar 

  36. Deng D et al. miR-137 acts as a tumor suppressor in astrocytoma by targeting RASGRF1. Tumour Biol. 2015.

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Yingwei Luo.

Ethics declarations

Conflicts of interests

None

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Luo, Y., Li, X., Dong, J. et al. microRNA-137 is downregulated in thyroid cancer and inhibits proliferation and invasion by targeting EGFR. Tumor Biol. 37, 7749–7755 (2016). https://doi.org/10.1007/s13277-015-4611-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-015-4611-8

Keywords

Navigation