Skip to main content

Advertisement

SpringerLink
Log in

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

  • Original Article
  • Published:
Pathology & Oncology Research

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).

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.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6

Similar content being viewed by others

References

  1. Kwan JYY, Psarianos P, Bruce JP, Yip KW, Liu F-F (2016) The complexity of microRNAs in human cancer. J Radiat Res. doi:10.1093/jrr/rrw009

    PubMed  PubMed Central  Google Scholar 

  2. Gyparaki M-T, Basdra EK, Papavassiliou AG (2014) MicroRNAs as regulatory elements in triple negative breast cancer. Cancer Lett 354:1–4

    Article  CAS  PubMed  Google Scholar 

  3. 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 17:21

    Article  PubMed  PubMed Central  Google Scholar 

  4. Arnedos M, Bihan C, Delaloge S, Andre F (2012) Triple-negative breast cancer: are we making headway at least? Ther Adv Med Oncol 4:195–210

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yadav BS, Chanana P, Jhamb S (2015) Biomarkers in triple negative breast cancer: a review. World J Clin Oncol 6:252–263

    Article  PubMed  PubMed Central  Google Scholar 

  6. 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 16:280–284

    Article  PubMed  Google Scholar 

  7. 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 7:167–173

    Article  PubMed  PubMed Central  Google Scholar 

  8. Zaleska K (2015) miRNA - therapeutic tool in breast cancer? Where are we now? Rep Pract Oncol Radiother 20:79–86

    Article  PubMed  Google Scholar 

  9. D’Ippolito E, Iorio MV (2013) MicroRNAs and triple negative breast cancer. Int J Mol Sci 14:22202–22220

    Article  PubMed  PubMed Central  Google Scholar 

  10. 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 15:87–89

    CAS  PubMed  PubMed Central  Google Scholar 

  11. 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) 38:433–442

    Article  Google Scholar 

  12. 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. 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 26:2126–2132

    Article  CAS  PubMed  Google Scholar 

  14. 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 15:498–504

    Article  CAS  PubMed  Google Scholar 

  15. 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 3:279–290

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. 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 34:4333–4346

    Article  CAS  PubMed  Google Scholar 

  17. 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 65:7065–7070

    Article  CAS  PubMed  Google Scholar 

  18. Zhang L, Long X (2015) Association of BRCA1 promoter methylation with sporadic breast cancers: evidence from 40 studies. Sci Rep 5:17869

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. 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 357:384–392

    Article  CAS  PubMed  Google Scholar 

  20. 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 6:13387–13401

    Article  PubMed  PubMed Central  Google Scholar 

  21. 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. 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 34:455–462

    Article  CAS  PubMed  Google Scholar 

  23. 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 150:916–922

    Article  PubMed  Google Scholar 

  24. 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 8:8671–8675

    CAS  PubMed  PubMed Central  Google Scholar 

  25. 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 72:335–345

    Article  CAS  PubMed  Google Scholar 

  26. 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. 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 100:453–464

    PubMed  Google Scholar 

  28. 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:e0141763

    Article  PubMed  PubMed Central  Google Scholar 

  29. 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 152:255–269

    Article  CAS  PubMed  Google Scholar 

  30. 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 439:275–279

    Article  CAS  PubMed  Google Scholar 

  31. 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 16:43–72

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. 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

    Google Scholar 

  33. 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 17:83

    Article  PubMed  PubMed Central  Google Scholar 

  34. 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 37:1421–1428

    Article  CAS  PubMed  Google Scholar 

  35. 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 19:299–308

    Article  CAS  PubMed  Google Scholar 

  36. 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. 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 528:204–211

    Article  CAS  PubMed  Google Scholar 

  38. 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

    Google Scholar 

  39. 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 27:5643–5647

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 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 134:41–51

    Article  CAS  PubMed  Google Scholar 

  41. 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 121:2750–2767

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank Fabrice Kwiatkowski for his help in analysis data by SEM software.

This research was funded by grants from the Laboratory of Biochemistry Research unit UR 12ES08 Cell Signaling and Disease of Faculty of Medicine of Monastir, the department of Pathology of Farhat Hached Hospital, the Molecular Oncology Laboratory of Center Jean Perrin in Clermont-Ferrand and the Fuda (Founding of the University of Auvergne).

Author information

Authors and Affiliations

  1. Departement of oncogenetics, Centre Jean Perrin, BP 392, 63011, Clermont-Ferrand, France

    Insaf Fkih M’hamed, Maud Privat & Yves-Jean Bignon

  2. EA4677 ERTICA, University of Auvergne, Clermont-Ferrand, France

    Insaf Fkih M’hamed, Maud Privat, Frédérique Penault-Llorca & Yves-Jean Bignon

  3. Laboratory of Biochemistry Research unit UR 12ES08 Cell Signaling and Disease, Faculty of Medicine of Monastir, University of Monastir, 5019, Monastir, Tunisia

    Insaf Fkih M’hamed & Abderraouf Kenani

  4. Department of Pathology, Farhat Hached Hospital, 4000, Sousse, Tunisia

    Mounir Trimeche

Authors
  1. Insaf Fkih M’hamed
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Maud Privat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Mounir Trimeche
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Frédérique Penault-Llorca
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yves-Jean Bignon
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Abderraouf Kenani
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Abderraouf Kenani.

Ethics declarations

We declare that this manuscript is original, has not been published before and is not currently being considered for publication elsewhere. We wish to confirm that there are no known conflicts of interest associated with this publication and there has been no significant financial support for this work that could have influenced its outcome. The manuscript has been read and approved by all named authors.

Competing Interests

The authors declare that they have no competing interests.

Ethics Approval and Consent to Participate

Ethics approval and consent was waived by the institutional review board of the Farhat-Hached Hospital of Sousse (Comité d’éthique et de Recherche du CHU Farhat-Hached).

Electronic supplementary material

ESM 1

(DOCX 10 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Fkih M’hamed, I., Privat, M., Trimeche, M. et al. miR-10b, miR-26a, miR-146a And miR-153 Expression in Triple Negative Vs Non Triple Negative Breast Cancer: Potential Biomarkers. Pathol. Oncol. Res. 23, 815–827 (2017). https://doi.org/10.1007/s12253-017-0188-4

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-017-0188-4

Keywords

Search

Navigation