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Published in: BMC Cancer 1/2014

Open Access 01-12-2014 | Research article

Oncogenic MicroRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum

Authors: Marek Sochor, Petra Basova, Michal Pesta, Nina Dusilkova, Jiri Bartos, Pavel Burda, Vit Pospisil, Tomas Stopka

Published in: BMC Cancer | Issue 1/2014

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Abstract

Background

MicroRNAs (miRs) represent a distinct class of posttranscriptional modulators of gene expression with remarkable stability in sera. Several miRs are oncogenic (oncomiRs) and are deregulated in the pathogenesis of breast cancer and function to inhibit tumor suppressors. Routine blood monitoring of these circulating tumor-derived products could be of significant benefit to the diagnosis and relapse detection of early-stage breast cancer (EBC) patients.

Methods

Aim of this project was to determine expression of miR-155, miR-19a, miR-181b, miR-24, relative to let-7a in sera of 63 patients with EBC and 21 healthy controls. Longitudinal multivariate data analysis was performed to stochastically model the serum levels of each of the oncomiRs during disease phases: from diagnosis, after surgery, and following chemo/radiotherapy. Moreover, this analysis was utilized to evaluate oncomiR levels in EBC patients subgrouped using current clinical prognostic factors including HER2, Ki-67, and grade III.

Results

EBC patients significantly over-express the oncomiRs at the time of diagnosis. Following surgical resection the serum levels of miR-155, miR-181b, and miR-24 significantly decreased (p = 1.89e-05, 5.41e-06, and 0.00638, respectively) whereas the miR-19a decreased significantly after the therapy (p = 0.00869). Furthermore, in case of high-risk patients serum levels of miR-155, miR-19a, miR-181b, and miR-24 are significantly more abundant in comparison to low-risk group (p = 0.026, 0.02567, 0.0250, and 0.00990) and show a decreasing trend upon therapy.

Conclusions

OncomiRs are significantly more abundant in the sera of EBC patients compared to controls at diagnosis. Differences in oncomiR levels reflecting EBC risk were also observed. Testing the oncomiRs may be useful for diagnostic purpose and possibly also for relapse detection in follow-up studies of EBC.
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Literature
2.
3.
go back to reference Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005, 65 (16): 7065-7070.CrossRefPubMed Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, Magri E, Pedriali M, Fabbri M, Campiglio M, Ménard S, Palazzo JP, Rosenberg A, Musiani P, Volinia S, Nenci I, Calin GA, Querzoli P, Negrini M, Croce CM: MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005, 65 (16): 7065-7070.CrossRefPubMed
4.
go back to reference Kim K, Chadalapaka G, Lee SO, Yamada D, Sastre-Garau X, Defossez PA, Park YY, Lee JS, Safe S: Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene. 2012, 31 (8): 1034-1044.CrossRefPubMed Kim K, Chadalapaka G, Lee SO, Yamada D, Sastre-Garau X, Defossez PA, Park YY, Lee JS, Safe S: Identification of oncogenic microRNA-17-92/ZBTB4/specificity protein axis in breast cancer. Oncogene. 2012, 31 (8): 1034-1044.CrossRefPubMed
5.
go back to reference Ouchida M, Kanzaki H, Ito S, Hanafusa H, Jitsumori Y, Tamaru S, Shimizu K: Novel direct targets of miR-19a identified in breast cancer cells by a quantitative proteomic approach. PLoS One. 2012, 7 (8): e44095-CrossRefPubMedPubMedCentral Ouchida M, Kanzaki H, Ito S, Hanafusa H, Jitsumori Y, Tamaru S, Shimizu K: Novel direct targets of miR-19a identified in breast cancer cells by a quantitative proteomic approach. PLoS One. 2012, 7 (8): e44095-CrossRefPubMedPubMedCentral
6.
go back to reference Li S, Yang C, Zhai L, Zhang W, Yu J, Gu F, Lang R, Fan Y, Gong M, Zhang X, Fu L: Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast. Breast Cancer Res Treat. 2012, 136 (1): 77-87.CrossRefPubMed Li S, Yang C, Zhai L, Zhang W, Yu J, Gu F, Lang R, Fan Y, Gong M, Zhang X, Fu L: Deep sequencing reveals small RNA characterization of invasive micropapillary carcinomas of the breast. Breast Cancer Res Treat. 2012, 136 (1): 77-87.CrossRefPubMed
7.
go back to reference Wu Q, Wang C, Lu Z, Guo L, Ge Q: Analysis of serum genome-wide microRNAs for breast cancer detection. Clini Chim Acta. 2012, 413 (13–14): 1058-1065.CrossRef Wu Q, Wang C, Lu Z, Guo L, Ge Q: Analysis of serum genome-wide microRNAs for breast cancer detection. Clini Chim Acta. 2012, 413 (13–14): 1058-1065.CrossRef
8.
go back to reference Song J, Bai Z, Han W, Zhang J, Meng H, Bi J, Ma X, Han S, Zhang Z: Identification of suitable reference genes for qPCR analysis of serum microRNA in gastric cancer patients. Dig Dis Sci. 2012, 57 (4): 897-904.CrossRefPubMed Song J, Bai Z, Han W, Zhang J, Meng H, Bi J, Ma X, Han S, Zhang Z: Identification of suitable reference genes for qPCR analysis of serum microRNA in gastric cancer patients. Dig Dis Sci. 2012, 57 (4): 897-904.CrossRefPubMed
9.
go back to reference Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S: A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS One. 2010, 5 (10): e13735-CrossRefPubMedPubMedCentral Zhao H, Shen J, Medico L, Wang D, Ambrosone CB, Liu S: A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS One. 2010, 5 (10): e13735-CrossRefPubMedPubMedCentral
10.
go back to reference Newman MA, Thomson JM, Hammond SM: Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA. 2008, 14 (8): 1539-1549.CrossRefPubMedPubMedCentral Newman MA, Thomson JM, Hammond SM: Lin-28 interaction with the Let-7 precursor loop mediates regulated microRNA processing. RNA. 2008, 14 (8): 1539-1549.CrossRefPubMedPubMedCentral
11.
go back to reference Kim SJ, Shin JY, Lee KD, Bae YK, Sung KW, Nam SJ, Chun KH: MicroRNA let-7a suppresses breast cancer cell migration and invasion through downregulation of C-C chemokine receptor type 7. Breast Cancer Res. 2012, 14 (1): R14-CrossRefPubMedPubMedCentral Kim SJ, Shin JY, Lee KD, Bae YK, Sung KW, Nam SJ, Chun KH: MicroRNA let-7a suppresses breast cancer cell migration and invasion through downregulation of C-C chemokine receptor type 7. Breast Cancer Res. 2012, 14 (1): R14-CrossRefPubMedPubMedCentral
12.
go back to reference Liu Y, Li H, Feng J, Cui X, Huang W, Li Y, Su F, Liu Q, Zhu J, Lv X, Chen J, Huang D, Yu F: Lin28 induces epithelial-to-mesenchymal transition and stemness via downregulation of Let-7a in breast cancer cells. PLoS One. 2013, 8 (12): e83083-CrossRefPubMedPubMedCentral Liu Y, Li H, Feng J, Cui X, Huang W, Li Y, Su F, Liu Q, Zhu J, Lv X, Chen J, Huang D, Yu F: Lin28 induces epithelial-to-mesenchymal transition and stemness via downregulation of Let-7a in breast cancer cells. PLoS One. 2013, 8 (12): e83083-CrossRefPubMedPubMedCentral
13.
go back to reference Cai WY, Wei TZ, Luo QC, Wu QW, Liu QF, Yang M, Ye GD, Wu JF, Chen YY, Sun GB, Liu YJ, Zhao WX, Zhang ZM, Li BA: The Wnt-beta-catenin pathway represses let-7 microRNA expression through transactivation of Lin28 to augment breast cancer stem cell expansion. J Cell Sci. 2013, 126 (Pt 13): 2877-2889.CrossRefPubMed Cai WY, Wei TZ, Luo QC, Wu QW, Liu QF, Yang M, Ye GD, Wu JF, Chen YY, Sun GB, Liu YJ, Zhao WX, Zhang ZM, Li BA: The Wnt-beta-catenin pathway represses let-7 microRNA expression through transactivation of Lin28 to augment breast cancer stem cell expansion. J Cell Sci. 2013, 126 (Pt 13): 2877-2889.CrossRefPubMed
14.
go back to reference Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, Liu MF, Wang ED: MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res. 2010, 70 (8): 3119-3127.CrossRefPubMed Jiang S, Zhang HW, Lu MH, He XH, Li Y, Gu H, Liu MF, Wang ED: MicroRNA-155 functions as an OncomiR in breast cancer by targeting the suppressor of cytokine signaling 1 gene. Cancer Res. 2010, 70 (8): 3119-3127.CrossRefPubMed
15.
go back to reference Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, Li J: Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One. 2012, 7 (10): e47003-CrossRefPubMedPubMedCentral Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, Li J: Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One. 2012, 7 (10): e47003-CrossRefPubMedPubMedCentral
16.
go back to reference Farazi TA, Horlings HM, Ten Hoeve JJ, Mihailovic A, Halfwerk H, Morozov P, Brown M, Hafner M, Reyal F, van Kouwenhove M, Kreike B, Sie D, Hovestadt V, Wessels LF, van de Vijver MJ, Tuschl T: MicroRNA sequence and expression analysis in breast tumors by deep sequencing. Cancer Res. 2011, 71 (13): 4443-4453.CrossRefPubMedPubMedCentral Farazi TA, Horlings HM, Ten Hoeve JJ, Mihailovic A, Halfwerk H, Morozov P, Brown M, Hafner M, Reyal F, van Kouwenhove M, Kreike B, Sie D, Hovestadt V, Wessels LF, van de Vijver MJ, Tuschl T: MicroRNA sequence and expression analysis in breast tumors by deep sequencing. Cancer Res. 2011, 71 (13): 4443-4453.CrossRefPubMedPubMedCentral
17.
go back to reference Bisso A, Faleschini M, Zampa F, Capaci V, De Santa J, Santarpia L, Piazza S, Cappelletti V, Daidone M, Agami R, Del Sal G: Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. Cell Cycle. 2013, 12 (11): 1679-1687.CrossRefPubMedPubMedCentral Bisso A, Faleschini M, Zampa F, Capaci V, De Santa J, Santarpia L, Piazza S, Cappelletti V, Daidone M, Agami R, Del Sal G: Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer. Cell Cycle. 2013, 12 (11): 1679-1687.CrossRefPubMedPubMedCentral
18.
go back to reference Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K: STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell. 2010, 39 (4): 493-506.CrossRefPubMedPubMedCentral Iliopoulos D, Jaeger SA, Hirsch HA, Bulyk ML, Struhl K: STAT3 activation of miR-21 and miR-181b-1 via PTEN and CYLD are part of the epigenetic switch linking inflammation to cancer. Mol Cell. 2010, 39 (4): 493-506.CrossRefPubMedPubMedCentral
19.
go back to reference Papadimitriou E, Vasilaki E, Vorvis C, Iliopoulos D, Moustakas A, Kardassis D, Stournaras C: Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-beta and miR-24: role in epithelial-to-mesenchymal transition. Oncogene. 2012, 31 (23): 2862-2875.CrossRefPubMed Papadimitriou E, Vasilaki E, Vorvis C, Iliopoulos D, Moustakas A, Kardassis D, Stournaras C: Differential regulation of the two RhoA-specific GEF isoforms Net1/Net1A by TGF-beta and miR-24: role in epithelial-to-mesenchymal transition. Oncogene. 2012, 31 (23): 2862-2875.CrossRefPubMed
20.
go back to reference Eichelser C, Flesch-Janys D, Chang-Claude J, Pantel K, Schwarzenbach H: Deregulated serum concentrations of circulating cell-free microRNAs miR-17, miR-34a, miR-155, and miR-373 in human breast cancer development and progression. Clin Chem. 2013, 59 (10): 1489-1496.CrossRefPubMed Eichelser C, Flesch-Janys D, Chang-Claude J, Pantel K, Schwarzenbach H: Deregulated serum concentrations of circulating cell-free microRNAs miR-17, miR-34a, miR-155, and miR-373 in human breast cancer development and progression. Clin Chem. 2013, 59 (10): 1489-1496.CrossRefPubMed
Metadata
Title
Oncogenic MicroRNAs: miR-155, miR-19a, miR-181b, and miR-24 enable monitoring of early breast cancer in serum
Authors
Marek Sochor
Petra Basova
Michal Pesta
Nina Dusilkova
Jiri Bartos
Pavel Burda
Vit Pospisil
Tomas Stopka
Publication date
01-12-2014
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2014
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/1471-2407-14-448

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