Skip to main content

Advertisement

SpringerLink
Log in

The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion

  • Original Paper
  • Published:
Medical Oncology Aims and scope Submit manuscript

Abstract

MicroRNA-21 (miR-21) overexpression is characteristic for various types of tumors, but it is still unknown whether its expression levels differ between invasive and non-invasive breast carcinomas. The main goal of the study was to determine the difference in miR-21 expression among normal tissue, non-invasive, invasive with non-invasive component, and pure invasive breast cancer samples, to explain its potential role and significance in breast cancer invasiveness. The second goal was to propose miR-21 as molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis. In order to reveal the role of miR-21 in breast cancer invasiveness, we measured miR-21 expression levels in 44 breast cancer and four normal samples by stem-loop real-time RT-PCR using TaqMan technology. Relative expression levels of miR-21 were significantly higher in invasive than in other groups (P = 0.002) and significantly higher in invasive compared with invasive with non-invasive component group in histological (P = 0.043) and nuclear grade 2 (P = 0.036), estrogen-receptor-positive (ER+) (P = 0.006), progesterone-receptor-positive (PR+) (P = 0.008), ER+PR+ (P = 0.007), and proliferation index (Ki-67) ≤ 20 % (P = 0.036) tumors. Our findings suggest that miR-21 could be independent molecular marker of breast cancer invasiveness and potential target for future anti-miR therapies for the prevention of invasion and metastasis.

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

Similar content being viewed by others

References

  1. Verkooijen HM, Fioretta GR, Vlastos G, Morabia A, Schubert H, Sappino A-P, et al. Important increase of invasive lobular breast cancer incidence in Geneva. Switzerland. Int J Cancer. 2003;104:778–81.

    Article  CAS  Google Scholar 

  2. Bair EL, Chen ML, McDaniel K, Sekiguchi K, Cress AE, Nagle RB, et al. Membrane type 1 matrix metalloprotease cleaves laminin-10 and promotes prostate cancer cell migration. Neoplasia. 2005;7:380–9.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  3. Ma L, Weinberg RA. Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet. 2008;24:448–56.

    Article  CAS  PubMed  Google Scholar 

  4. Xia M, Hu M. The role of microRNA in tumor invasion and metastasis. J Cancer Mol. 2010;5:33–9.

    CAS  Google Scholar 

  5. Farabegoli F, Champeme MH, Bieche I, Santini D, Ceccarelli C, Derenzini M, et al. Genetic pathways in the evolution of breast ductal carcinoma in situ. J Pathol. 2002;196:280–6.

    Article  PubMed  Google Scholar 

  6. Wong H, Lau S, Yau T, Cheung P, Epstein RJ. Presence of an in situ component is associated with reduced biological aggressiveness of size-matched invasive breast cancer. B J Cancer. 2010;102:1391–6.

    Article  CAS  Google Scholar 

  7. Hannemann J, Velds A, Halfwerk JBG, Kreike B, Peterse JL, van de Vijver MJ. Classification of ductal carcinoma in situ by gene expression profiling. Breast Cancer Res. 2006;8:61–80.

    Article  Google Scholar 

  8. Chuang JC, Jones PA. Epigenetics and microRNAs. Pediatr Res. 2007;61(5 Part 2):24R.

    Article  CAS  PubMed  Google Scholar 

  9. Wu W, Lin Z, Zhuang Z, Liang X. Expression profile of mammalian microRNAs in endometrioid adenocarcinoma. Eur J Cancer Prev. 2009;18:50–5.

    Article  CAS  PubMed  Google Scholar 

  10. Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.

    Article  CAS  PubMed  Google Scholar 

  11. Song B, Wang C, Liu J, Wang X, Lv L, Wei L, et al. MicroRNA-21 regulates breast cancer invasion partly by targeting tissue inhibitor of metalloproteinase 3 expression. J Exp Clinl Cancer Res. 2010;29:29–36.

    Article  CAS  Google Scholar 

  12. Huang G-L, Zhang X-H, Guo G-L, Huang K-T, Yang K-Y, Shen X, et al. Clinical significance of miR-21 expression in breast cancer: SYBR-Green I-based real-time RT-PCR study of invasive ductal carcinoma. Oncol Rep. 2009;21:673–9.

    CAS  PubMed  Google Scholar 

  13. Lee JA, Lee HY, Lee ES, Kim I, Bae JW. Prognostic implications of microRNA-21 overexpression in invasive ductal carcinomas of the breast. J Breast Cancer. 2011;14:269–75.

    Article  PubMed Central  PubMed  Google Scholar 

  14. Zhu S, Si ML, Wu H, Mo YY. MicroRNA-21 targets the tumor suppressor gene tropomyosin 1 (TPM1). J Biol Chem. 2007;282:14328–36.

    Article  CAS  PubMed  Google Scholar 

  15. Yang Y, Chaerkady R, Beer MA, Mendell JT, Pandey A. Identification of miR-21 targets in breast cancer cells using a quantitative proteomic approach. Proteomics. 2009;9:1374–84.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  16. Span PN, Lindberg RLP, Manders P, Tjan-Heijnen VCG, Heuvel JJTM, Beex LVAM, et al. Tissue inhibitors of metalloproteinase expression in human breast cancer: TIMP-3 is associated with adjuvant endocrine therapy success. J Path. 2004;202:395–402.

    Article  CAS  PubMed  Google Scholar 

  17. Mylona E, Magkou C, Giannopoulou I, Agrogiannis G, Markaki S, Keramopoulos A, et al. Breast Cancer Res. 2006;8:R57–64.

    Article  PubMed Central  PubMed  Google Scholar 

  18. Lopez-Camarillo C, Fonseca-Sánchez MA, Flores-Pérez A, Marchat LA, Arechaga-Ocampo E, Azuara-Liceaga E, et al. Functional roles of microRNAs in cancer: microRNomes and oncomiRs connection. In: Lopez-Camarillo CAL, Arechaga-Ocampo E, Azuara-Liceaga E, Perez Plasencia C, Fuentes-Mera L, et al., editors. Oncogenomics and cancer proteomics—novel approaches in biomarkers discovery and therapeutic targets in cancer. InTech; 2013. p. 72–89.

  19. Yoshinaga H, Matsuhashi S, Fujiyama C, Masaki Z. Novel human PDCD4 (H731) gene expressed in proliferative cells is expressed in the small duct epithelial cells of the breast as revealed by an anti-H731 antibody. Pathol Int. 1999;49:1067–77.

    Article  CAS  PubMed  Google Scholar 

  20. Frankel LB, Christoffersen NR, Jacobsen A, Lindow M, Krogh A, Lund AH. Programmed cell death 4 (PDCD4) Is an important functional target of the microRNA miR-21 in breast cancer cells. J Biol Chem. 2007;283:1026–33.

    Article  PubMed  Google Scholar 

  21. Yu Z, Baserga R, Chen L, Wang C, Lisanti MP, Pestell RG. microRNA, cell cycle, and human breast cancer. Am J Path. 2010;176:1058–64.

    Article  CAS  PubMed  Google Scholar 

  22. Tang J, Ahmad A, Sarkar FH. The role of microRNAs in breast cancer migration, invasion and metastasis. Int J Mol Sci. 2012;13:13414–37.

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  23. Leake R. Immunohistochemical detection of steroid receptors in breast cancer: a working protocol. J Clin Pathol. 2000;53:634–5.

    Article  CAS  PubMed  Google Scholar 

  24. Sauter G, Lee J, Bartlett JMS, Slamon DJ, Press MF. Guidelines for human epidermal growth factor receptor 2 testing: biologic and methodologic considerations. J Clin Oncol. 2009;27:1323–33.

    Article  CAS  PubMed  Google Scholar 

  25. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.

    Article  CAS  PubMed  Google Scholar 

  26. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. MiR-21-mediated tumor growth. Oncogene. 2006;26:2799–803.

    Article  PubMed  Google Scholar 

  27. Li J, Zhang Y, Zhang W, Jia S, Tian R, Kang Y, et al. Genetic heterogeneity of breast cancer metastasis may be related to miR-21 regulation of TIMP-3 in translation. Int J Surg Oncol. 2013;2013:1–7.

    Article  Google Scholar 

  28. Liu YE. Preparation and characterization of recombinant tissue inhibitor of metalloproteinase 4 (TIMP-4). J Biol Chem. 1997;272:20479–83.

    Article  CAS  PubMed  Google Scholar 

  29. Qian B, Katsaros D, Lu L, Preti M, Durando A, Arisio R, et al. High miR-21 expression in breast cancer associated with poor disease-free survival in early stage disease and high TGF-β1. Breast Cancer Res Treat. 2008;117:131–40.

    Article  PubMed  Google Scholar 

  30. Si H, Sun X, Chen Y, Cao Y, Chen S, Wang H, et al. Circulating microRNA-92a and microRNA-21 as novel minimally invasive biomarkers for primary breast cancer. J Cancer Res Clin Oncol. 2012;139:223–9.

    Article  PubMed Central  PubMed  Google Scholar 

  31. Kumar SKR, Pazhanimuthu A, Perumal P. Overexpression of circulating miRNA-21 and miRNA-146a in plasma samples of breast cancer patients. Indian J Biochem Biophys. 2013;50:210–4.

    CAS  PubMed  Google Scholar 

  32. Kumarswamy R, Volkmann I, Thum T. Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011;8:706–13.

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This work was supported by the Ministry of Education and Science, Republic of Serbia, Grant ON173049 (Nina Petrović, Vesna Mandušić, Boban Stanojević, Silvana Lukić, Lidija Todorović, Bogomir Dimitrijević). We thank Radoslav Davidović for valuable technical support.

Conflict of interest

All authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Vinča Institute of Nuclear Sciences, University of Belgrade, Mike Petrovića Alasa 12-14, 11001, Belgrade, Serbia

    Nina Petrović, Vesna Mandušić, Boban Stanojević, Lidija Todorović & Bogomir Dimitrijević

  2. Institute for Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia

    Silvana Lukić

  3. Department of Pharmacology, Faculty of Dentistry, University of Belgrade, Dr. Subotića 8, 11000, Belgrade, Serbia

    Jelena Roganović

Authors
  1. Nina Petrović
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vesna Mandušić
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Boban Stanojević
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Silvana Lukić
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lidija Todorović
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Jelena Roganović
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Bogomir Dimitrijević
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nina Petrović.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (DOC 51 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Petrović, N., Mandušić, V., Stanojević, B. et al. The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion. Med Oncol 31, 867 (2014). https://doi.org/10.1007/s12032-014-0867-x

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1007/s12032-014-0867-x

Keywords

Search

Navigation