Skip to main content
Top
Published in: Pathology & Oncology Research 4/2017

01-10-2017 | Original Article

miR-10b, miR-26a, miR-146a And miR-153 Expression in Triple Negative Vs Non Triple Negative Breast Cancer: Potential Biomarkers

Authors: Insaf Fkih M’hamed, Maud Privat, Mounir Trimeche, Frédérique Penault-Llorca, Yves-Jean Bignon, Abderraouf Kenani

Published in: Pathology & Oncology Research | Issue 4/2017

Login to get access

Abstract

MicroRNAs (miRNAs) are small non-coding RNAs composed of 18–25 nucleotides that can post-transcriptionally regulate gene expression and have key regulatory roles in cancer, acting as both oncogenes and tumor suppressors. About 1000 genes in humans encode miRNAs, which account for approximately 3% of the human genome, and up to 30% of human protein coding genes may be regulated by miRNAs. The objective of this article is to evaluate the expression profile of four miRNAs previously implicated in triple negative breast cancer: miR-10b, miR-26a, miR-146a and miR-153, and to determine their possible interaction in triple negative and non triple negative breast cancer based on clinical outcome and the expression of BRCA1. 24 triple-negative and 13 non triple negative breast cancer cases, were studied by q-RT-PCR and immunohistochemistry to determine the expression of the four studied miRNAs and the BRCA1 protein, respectively. We observed that the BRCA1 protein was absent in 62.5% of the triple negative cases. Besides, the miR-146a and miR-26a were over expressed in triple negative breast cancer. These two miRNAs, miR-10b and miR-153 were significantly associated to lymph node metastases occurrence in triple negative breast carcinoma. All the analyzed microRNAs were not associated with the expression of BRCA1 in our conditions. Our work provides evidence that miR-146a, miR-26a, miR-10b and miR-153 could be defined as biomarkers in triple negative breast cancer to predict lymph node metastases (LNM).
Appendix
Available only for authorised users
Literature
2.
go back to reference Gyparaki M-T, Basdra EK, Papavassiliou AG (2014) MicroRNAs as regulatory elements in triple negative breast cancer. Cancer Lett 354:1–4CrossRefPubMed Gyparaki M-T, Basdra EK, Papavassiliou AG (2014) MicroRNAs as regulatory elements in triple negative breast cancer. Cancer Lett 354:1–4CrossRefPubMed
3.
go back to reference van Schooneveld E, Wildiers H, Vergote I, Vermeulen PB, Dirix LY, Van Laere SJ (2015) Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management. Breast Cancer Res 17:21CrossRefPubMedPubMedCentral van Schooneveld E, Wildiers H, Vergote I, Vermeulen PB, Dirix LY, Van Laere SJ (2015) Dysregulation of microRNAs in breast cancer and their potential role as prognostic and predictive biomarkers in patient management. Breast Cancer Res 17:21CrossRefPubMedPubMedCentral
6.
go back to reference Andrés R, Pajares I, Balmaña J, Llort G, Ramón Y, Cajal T, Chirivella I et al (2014) Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC). Clin Transl Oncol 16:280–284CrossRefPubMed Andrés R, Pajares I, Balmaña J, Llort G, Ramón Y, Cajal T, Chirivella I et al (2014) Association of BRCA1 germline mutations in young onset triple-negative breast cancer (TNBC). Clin Transl Oncol 16:280–284CrossRefPubMed
7.
go back to reference Qiu J, Xue X, Hu C, Xu H, Kou D, Li R et al (2016) Comparison of clinicopathological features and prognosis in triple-negative and non-triple negative breast cancer. J Cancer 7:167–173CrossRefPubMedPubMedCentral Qiu J, Xue X, Hu C, Xu H, Kou D, Li R et al (2016) Comparison of clinicopathological features and prognosis in triple-negative and non-triple negative breast cancer. J Cancer 7:167–173CrossRefPubMedPubMedCentral
8.
go back to reference Zaleska K (2015) miRNA - therapeutic tool in breast cancer? Where are we now? Rep Pract Oncol Radiother 20:79–86CrossRefPubMed Zaleska K (2015) miRNA - therapeutic tool in breast cancer? Where are we now? Rep Pract Oncol Radiother 20:79–86CrossRefPubMed
10.
go back to reference Popovska-Jankovic K, Noveski P, Chakalova L, Petrusevska G, Kubelka K, Plaseska-Karanfilska D (2012) MicroRNAs in breast cancer -our initial results. Balkan J Med Genet 15:87–89PubMedPubMedCentral Popovska-Jankovic K, Noveski P, Chakalova L, Petrusevska G, Kubelka K, Plaseska-Karanfilska D (2012) MicroRNAs in breast cancer -our initial results. Balkan J Med Genet 15:87–89PubMedPubMedCentral
11.
go back to reference Fkih M’hamed I, Privat M, Ponelle F, Penault-Llorca F, Kenani A, Bignon Y-J (2015) Identification of miR-10b, miR-26a, miR-146a and miR-153 as potential triple-negative breast cancer biomarkers. Cell Oncol (Dordr) 38:433–442CrossRef Fkih M’hamed I, Privat M, Ponelle F, Penault-Llorca F, Kenani A, Bignon Y-J (2015) Identification of miR-10b, miR-26a, miR-146a and miR-153 as potential triple-negative breast cancer biomarkers. Cell Oncol (Dordr) 38:433–442CrossRef
12.
go back to reference Kwiatkowski F, Girard M, Hacene K, Berlie J. 2000. [Sem: A suitable statistical software adaptated for research in oncology]. Bull Cancer.;87:715–21 Kwiatkowski F, Girard M, Hacene K, Berlie J. 2000. [Sem: A suitable statistical software adaptated for research in oncology]. Bull Cancer.;87:715–21
13.
go back to reference Turner NC, Reis-Filho JS, Russell AM, Springall RJ, Ryder K, Steele D et al (2007) BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene 26:2126–2132CrossRefPubMed Turner NC, Reis-Filho JS, Russell AM, Springall RJ, Ryder K, Steele D et al (2007) BRCA1 dysfunction in sporadic basal-like breast cancer. Oncogene 26:2126–2132CrossRefPubMed
14.
go back to reference Yamashita N, Tokunaga E, Kitao H, Hitchins M, Inoue Y, Tanaka K et al (2015) Epigenetic inactivation of BRCA1 through promoter hypermethylation and its clinical importance in triple-negative breast cancer. Clin Breast Cancer 15:498–504CrossRefPubMed Yamashita N, Tokunaga E, Kitao H, Hitchins M, Inoue Y, Tanaka K et al (2015) Epigenetic inactivation of BRCA1 through promoter hypermethylation and its clinical importance in triple-negative breast cancer. Clin Breast Cancer 15:498–504CrossRefPubMed
15.
go back to reference Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS et al (2011) Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med 3:279–290CrossRefPubMedPubMedCentral Garcia AI, Buisson M, Bertrand P, Rimokh R, Rouleau E, Lopez BS et al (2011) Down-regulation of BRCA1 expression by miR-146a and miR-146b-5p in triple negative sporadic breast cancers. EMBO Mol Med 3:279–290CrossRefPubMedPubMedCentral
16.
go back to reference Kumaraswamy E, Wendt KL, Augustine LA, Stecklein SR, Sibala EC, Li D et al (2015) BRCA1 regulation of epidermal growth factor receptor (EGFR) expression in human breast cancer cells involves microRNA-146a and is critical for its tumor suppressor function. Oncogene 34:4333–4346CrossRefPubMed Kumaraswamy E, Wendt KL, Augustine LA, Stecklein SR, Sibala EC, Li D et al (2015) BRCA1 regulation of epidermal growth factor receptor (EGFR) expression in human breast cancer cells involves microRNA-146a and is critical for its tumor suppressor function. Oncogene 34:4333–4346CrossRefPubMed
17.
go back to reference Iorio MV, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sabbioni S et al (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070CrossRefPubMed Iorio MV, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sabbioni S et al (2005) MicroRNA gene expression deregulation in human breast cancer. Cancer Res 65:7065–7070CrossRefPubMed
19.
go back to reference Liu P, Tang H, Chen B, He Z, Deng M, Wu M et al (2015) miR-26a suppresses tumour proliferation and metastasis by targeting metadherin in triple negative breast cancer. Cancer Lett 357:384–392CrossRefPubMed Liu P, Tang H, Chen B, He Z, Deng M, Wu M et al (2015) miR-26a suppresses tumour proliferation and metastasis by targeting metadherin in triple negative breast cancer. Cancer Lett 357:384–392CrossRefPubMed
20.
go back to reference Stückrath I, Rack B, Janni W, Jäger B, Pantel K, Schwarzenbach H (2015) Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients. Oncotarget 6:13387–13401CrossRefPubMedPubMedCentral Stückrath I, Rack B, Janni W, Jäger B, Pantel K, Schwarzenbach H (2015) Aberrant plasma levels of circulating miR-16, miR-107, miR-130a and miR-146a are associated with lymph node metastasis and receptor status of breast cancer patients. Oncotarget 6:13387–13401CrossRefPubMedPubMedCentral
21.
go back to reference Rask L, Balslev E, Søkilde R, Høgdall E, Flyger H, Eriksen J, et al.. 2014. Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status. Cell Oncol (Dordr); 37:215–27 Rask L, Balslev E, Søkilde R, Høgdall E, Flyger H, Eriksen J, et al.. 2014. Differential expression of miR-139, miR-486 and miR-21 in breast cancer patients sub-classified according to lymph node status. Cell Oncol (Dordr); 37:215–27
22.
go back to reference Chen W, Cai F, Zhang B, Barekati Z, Zhong XY (2013) The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumour Biol 34:455–462CrossRefPubMed Chen W, Cai F, Zhang B, Barekati Z, Zhong XY (2013) The level of circulating miRNA-10b and miRNA-373 in detecting lymph node metastasis of breast cancer: potential biomarkers. Tumour Biol 34:455–462CrossRefPubMed
23.
go back to reference Nakata K, Ohuchida K, Mizumoto K, Kayashima T, Ikenaga N, Sakai H et al (2011) MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis. Surgery 150:916–922CrossRefPubMed Nakata K, Ohuchida K, Mizumoto K, Kayashima T, Ikenaga N, Sakai H et al (2011) MicroRNA-10b is overexpressed in pancreatic cancer, promotes its invasiveness, and correlates with a poor prognosis. Surgery 150:916–922CrossRefPubMed
24.
go back to reference Chen W-J, Zhang E-N, Zhong Z-K, Jiang M-Z, Yang X-F, Zhou D-M et al (2015) MicroRNA-153 expression and prognosis in non-small cell lung cancer. Int J Clin Exp Pathol 8:8671–8675PubMedPubMedCentral Chen W-J, Zhang E-N, Zhong Z-K, Jiang M-Z, Yang X-F, Zhou D-M et al (2015) MicroRNA-153 expression and prognosis in non-small cell lung cancer. Int J Clin Exp Pathol 8:8671–8675PubMedPubMedCentral
25.
go back to reference Bao B, Ali S, Banerjee S, Wang Z, Logna F, Azmi AS et al (2012) Curcumin analogue CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression. Cancer Res 72:335–345CrossRefPubMed Bao B, Ali S, Banerjee S, Wang Z, Logna F, Azmi AS et al (2012) Curcumin analogue CDF inhibits pancreatic tumor growth by switching on suppressor microRNAs and attenuating EZH2 expression. Cancer Res 72:335–345CrossRefPubMed
26.
go back to reference Visani M, de Biase D, Marucci G, Cerasoli S, Nigrisoli E, Bacchi Reggiani ML, et al.. 2014. Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III. Mol Oncol. 8:417–30 Visani M, de Biase D, Marucci G, Cerasoli S, Nigrisoli E, Bacchi Reggiani ML, et al.. 2014. Expression of 19 microRNAs in glioblastoma and comparison with other brain neoplasia of grades I-III. Mol Oncol. 8:417–30
27.
go back to reference Gonçalves A, Sabatier R, Charafe-Jauffret E, Gilabert M, Provansal M, Tarpin C et al (2013) Triple-negative breast cancer: histoclinical and molecular features, therapeutic management and perspectives. Bull Cancer 100:453–464PubMed Gonçalves A, Sabatier R, Charafe-Jauffret E, Gilabert M, Provansal M, Tarpin C et al (2013) Triple-negative breast cancer: histoclinical and molecular features, therapeutic management and perspectives. Bull Cancer 100:453–464PubMed
28.
go back to reference Cossu-Rocca P, Orrù S, Muroni MR, Sanges F, Sotgiu G, Ena S et al (2015) Analysis of PIK3CA mutations and activation pathways in triple negative breast cancer. PLoS One 10:e0141763CrossRefPubMedPubMedCentral Cossu-Rocca P, Orrù S, Muroni MR, Sanges F, Sotgiu G, Ena S et al (2015) Analysis of PIK3CA mutations and activation pathways in triple negative breast cancer. PLoS One 10:e0141763CrossRefPubMedPubMedCentral
29.
go back to reference Wang J, Zhang C, Chen K, Tang H, Tang J, Song C et al (2015) ERβ1 inversely correlates with PTEN/PI3K/AKT pathway and predicts a favorable prognosis in triple-negative breast cancer. Breast Cancer Res Treat 152:255–269CrossRefPubMed Wang J, Zhang C, Chen K, Tang H, Tang J, Song C et al (2015) ERβ1 inversely correlates with PTEN/PI3K/AKT pathway and predicts a favorable prognosis in triple-negative breast cancer. Breast Cancer Res Treat 152:255–269CrossRefPubMed
30.
go back to reference Park YH, Jung HH, Ahn JS, Im Y-H (2013) Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K pathway. Biochem Biophys Res Commun 439:275–279CrossRefPubMed Park YH, Jung HH, Ahn JS, Im Y-H (2013) Statin induces inhibition of triple negative breast cancer (TNBC) cells via PI3K pathway. Biochem Biophys Res Commun 439:275–279CrossRefPubMed
31.
go back to reference De P, Sun Y, Carlson JH, Friedman LS, Leyland-Jones BR, Dey N (2014) Doubling down on the PI3K-AKT-mTOR pathway enhances the antitumor efficacy of PARP inhibitor in triple negative breast cancer model beyond BRCA-ness. Neoplasia 16:43–72CrossRefPubMedPubMedCentral De P, Sun Y, Carlson JH, Friedman LS, Leyland-Jones BR, Dey N (2014) Doubling down on the PI3K-AKT-mTOR pathway enhances the antitumor efficacy of PARP inhibitor in triple negative breast cancer model beyond BRCA-ness. Neoplasia 16:43–72CrossRefPubMedPubMedCentral
32.
go back to reference Li J, Song Z, Wang Y, Yin Y, Liu Y, Yuan R et al (2016) Overexpression of SphK1 enhances cell proliferation and invasion in triple-negative breast cancer via the PI3K/AKT signaling pathway. Tumour Biol. doi:10.1007/s13277-016-4954-9 Li J, Song Z, Wang Y, Yin Y, Liu Y, Yuan R et al (2016) Overexpression of SphK1 enhances cell proliferation and invasion in triple-negative breast cancer via the PI3K/AKT signaling pathway. Tumour Biol. doi:10.​1007/​s13277-016-4954-9
33.
go back to reference Phua YW, Nguyen A, Roden DL, Elsworth B, Deng N, Nikolic I et al (2015) MicroRNA profiling of the pubertal mouse mammary gland identifies miR-184 as a candidate breast tumour suppressor gene. Breast Cancer Res 17:83CrossRefPubMedPubMedCentral Phua YW, Nguyen A, Roden DL, Elsworth B, Deng N, Nikolic I et al (2015) MicroRNA profiling of the pubertal mouse mammary gland identifies miR-184 as a candidate breast tumour suppressor gene. Breast Cancer Res 17:83CrossRefPubMedPubMedCentral
34.
go back to reference Wang F, Li L, Chen Z, Zhu M, Gu Y (2016) MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway. Int J Mol Med 37:1421–1428CrossRefPubMed Wang F, Li L, Chen Z, Zhu M, Gu Y (2016) MicroRNA-214 acts as a potential oncogene in breast cancer by targeting the PTEN-PI3K/Akt signaling pathway. Int J Mol Med 37:1421–1428CrossRefPubMed
35.
go back to reference Xu J-F, Zhang S-J, Zhao C, Qiu B-S, Gu H-F, Hong J-F et al (2015) Altered microRNA expression profile in synovial fluid from patients with knee osteoarthritis with treatment of hyaluronic acid. Mol Diagn Ther 19:299–308CrossRefPubMed Xu J-F, Zhang S-J, Zhao C, Qiu B-S, Gu H-F, Hong J-F et al (2015) Altered microRNA expression profile in synovial fluid from patients with knee osteoarthritis with treatment of hyaluronic acid. Mol Diagn Ther 19:299–308CrossRefPubMed
36.
go back to reference Chai Z-T, Zhu X-D, Ao J-Y, Wang W-Q, Gao D-M, Kong J, et al.. 2015. microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol; 8:56 Chai Z-T, Zhu X-D, Ao J-Y, Wang W-Q, Gao D-M, Kong J, et al.. 2015. microRNA-26a suppresses recruitment of macrophages by down-regulating macrophage colony-stimulating factor expression through the PI3K/Akt pathway in hepatocellular carcinoma. J Hematol Oncol; 8:56
37.
go back to reference Song L, Duan P, Guo P, Li D, Li S, Xu Y et al (2012) Downregulation of miR-223 and miR-153 mediates mechanical stretch-stimulated proliferation of venous smooth muscle cells via activation of the insulin-like growth factor-1 receptor. Arch Biochem Biophys 528:204–211CrossRefPubMed Song L, Duan P, Guo P, Li D, Li S, Xu Y et al (2012) Downregulation of miR-223 and miR-153 mediates mechanical stretch-stimulated proliferation of venous smooth muscle cells via activation of the insulin-like growth factor-1 receptor. Arch Biochem Biophys 528:204–211CrossRefPubMed
38.
go back to reference Chen Z-J, Wei W, Jiang G-M, Liu H, Wei W-D, Yang X et al (2016) Activation of GPER suppresses epithelial mesenchymal transition of triple negative breast cancer cells via NF-κB signals. Mol Oncol. doi:10.1016/j.molonc.2016.01.002 Chen Z-J, Wei W, Jiang G-M, Liu H, Wei W-D, Yang X et al (2016) Activation of GPER suppresses epithelial mesenchymal transition of triple negative breast cancer cells via NF-κB signals. Mol Oncol. doi:10.​1016/​j.​molonc.​2016.​01.​002
39.
go back to reference Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC (2008) Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27:5643–5647CrossRefPubMedPubMedCentral Bhaumik D, Scott GK, Schokrpur S, Patil CK, Campisi J, Benz CC (2008) Expression of microRNA-146 suppresses NF-kappaB activity with reduction of metastatic potential in breast cancer cells. Oncogene 27:5643–5647CrossRefPubMedPubMedCentral
40.
go back to reference Tanic M, Zajac M, Gómez-López G, Benítez J, Martínez-Delgado B (2012) Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFκB pathway. Breast Cancer Res Treat 134:41–51CrossRefPubMed Tanic M, Zajac M, Gómez-López G, Benítez J, Martínez-Delgado B (2012) Integration of BRCA1-mediated miRNA and mRNA profiles reveals microRNA regulation of TRAF2 and NFκB pathway. Breast Cancer Res Treat 134:41–51CrossRefPubMed
41.
go back to reference Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y et al (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767CrossRefPubMedPubMedCentral Lehmann BD, Bauer JA, Chen X, Sanders ME, Chakravarthy AB, Shyr Y et al (2011) Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J Clin Invest 121:2750–2767CrossRefPubMedPubMedCentral
Metadata
Title
miR-10b, miR-26a, miR-146a And miR-153 Expression in Triple Negative Vs Non Triple Negative Breast Cancer: Potential Biomarkers
Authors
Insaf Fkih M’hamed
Maud Privat
Mounir Trimeche
Frédérique Penault-Llorca
Yves-Jean Bignon
Abderraouf Kenani
Publication date
01-10-2017
Publisher
Springer Netherlands
Published in
Pathology & Oncology Research / Issue 4/2017
Print ISSN: 1219-4956
Electronic ISSN: 1532-2807
DOI
https://doi.org/10.1007/s12253-017-0188-4

Other articles of this Issue 4/2017

Pathology & Oncology Research 4/2017 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine