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Published in: Medical Oncology 3/2014

01-03-2014 | Original Paper

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

Authors: Nina Petrović, Vesna Mandušić, Boban Stanojević, Silvana Lukić, Lidija Todorović, Jelena Roganović, Bogomir Dimitrijević

Published in: Medical Oncology | Issue 3/2014

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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.
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Literature
1.
go back to reference 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.CrossRef 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.CrossRef
2.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
3.
go back to reference Ma L, Weinberg RA. Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet. 2008;24:448–56.PubMedCrossRef Ma L, Weinberg RA. Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet. 2008;24:448–56.PubMedCrossRef
4.
go back to reference Xia M, Hu M. The role of microRNA in tumor invasion and metastasis. J Cancer Mol. 2010;5:33–9. Xia M, Hu M. The role of microRNA in tumor invasion and metastasis. J Cancer Mol. 2010;5:33–9.
5.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
6.
go back to reference 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.CrossRef 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.CrossRef
7.
go back to reference 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.CrossRef 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.CrossRef
9.
go back to reference Wu W, Lin Z, Zhuang Z, Liang X. Expression profile of mammalian microRNAs in endometrioid adenocarcinoma. Eur J Cancer Prev. 2009;18:50–5.PubMedCrossRef Wu W, Lin Z, Zhuang Z, Liang X. Expression profile of mammalian microRNAs in endometrioid adenocarcinoma. Eur J Cancer Prev. 2009;18:50–5.PubMedCrossRef
10.
go back to reference Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.PubMedCrossRef Shenouda SK, Alahari SK. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28:369–78.PubMedCrossRef
11.
go back to reference 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.CrossRef 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.CrossRef
12.
go back to reference 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.PubMed 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.PubMed
13.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
14.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
15.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
16.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
18.
go back to reference 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. 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.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
20.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
21.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
23.
go back to reference Leake R. Immunohistochemical detection of steroid receptors in breast cancer: a working protocol. J Clin Pathol. 2000;53:634–5.PubMedCrossRef Leake R. Immunohistochemical detection of steroid receptors in breast cancer: a working protocol. J Clin Pathol. 2000;53:634–5.PubMedCrossRef
24.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
25.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
26.
27.
go back to reference 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.CrossRef 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.CrossRef
28.
go back to reference Liu YE. Preparation and characterization of recombinant tissue inhibitor of metalloproteinase 4 (TIMP-4). J Biol Chem. 1997;272:20479–83.PubMedCrossRef Liu YE. Preparation and characterization of recombinant tissue inhibitor of metalloproteinase 4 (TIMP-4). J Biol Chem. 1997;272:20479–83.PubMedCrossRef
29.
go back to reference 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.PubMedCrossRef 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.PubMedCrossRef
30.
go back to reference 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.PubMedCentralPubMedCrossRef 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.PubMedCentralPubMedCrossRef
31.
go back to reference 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.PubMed 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.PubMed
32.
go back to reference Kumarswamy R, Volkmann I, Thum T. Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011;8:706–13.PubMedCrossRef Kumarswamy R, Volkmann I, Thum T. Regulation and function of miRNA-21 in health and disease. RNA Biol. 2011;8:706–13.PubMedCrossRef
Metadata
Title
The difference in miR-21 expression levels between invasive and non-invasive breast cancers emphasizes its role in breast cancer invasion
Authors
Nina Petrović
Vesna Mandušić
Boban Stanojević
Silvana Lukić
Lidija Todorović
Jelena Roganović
Bogomir Dimitrijević
Publication date
01-03-2014
Publisher
Springer US
Published in
Medical Oncology / Issue 3/2014
Print ISSN: 1357-0560
Electronic ISSN: 1559-131X
DOI
https://doi.org/10.1007/s12032-014-0867-x

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