Molecular Biology Reports

, Volume 46, Issue 2, pp 1787–1796 | Cite as

The role of miRNAs as a predictor of multicentricity in breast cancer

  • Huseyin Akbulut
  • Yeliz Emine ErsoyEmail author
  • Ender CoskunpinarEmail author
  • Zuhal Gucin
  • Seyma Yildiz
  • Fatma Umit Malya
  • Burcu Hasturk
  • Mahmut Muslumanoglu
Original Article


Expression profiles of miRNAs are shown to be different in various cancers to regulate expression of mRNA or to have a role in inhibition of translation, thus it shows the possible effect in progression, invasion and metastasis of breast cancer cells. The effect of breast conserving treatment in local recurrence and survival rates for the patients who have multicentric breast cancer is still controversial. In our study, we intended to evaluate the foresight of 84 miRNAs which are identified in breast cancer for having differentiated expressions. Thirty-one patients with unifocal and 26 patients with multicentric breast cancer were included in this study. These tissue samples of both malignant and normal breast tissues were kept in RNA later solution at − 80 °C. Eighty-four miRNAs were studied with miScript miRNA PCR Array Human Breast Cancer kit. Fold change, cut off value was accepted as four. In unifocal group, there were 13 upregulated and five downregulated miRNAs and in multicentric group, there were three upregulated and seven downregulated miRNAs. To reach better results for breast cancer diagnosis and treatment, it is important to enlighten tumor biology, and pay attention to target and individual therapy. Thus, miRNAs have potential role in identifying tumor characteristics in supporting diagnosis and resulting with better evaluated disease for better treatment results with individual strategies.


Breast cancer Expression MicroRNAs Multicentric Multifocal 



This research was supported by the Scientific Research Projects Unit of Bezmialem Vakif University (Project No.: BVU 12.2013/7).

Compliance with ethical standards

Conflict of interest

No conflict of interest was declared by the authors.

Ethical approval

This study was reviewed and approved by Ethics Committee of Bezmialem Vakıf University, School of Medicine (11.27.2013/no:1206642/050/01/04/231). Each patient involved in this study gave written informed consent.


  1. 1.
    Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 23 136(2):215–233. CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Siegel R, Naishadham D, Jemal A (2013) Cancer statistics, 2013. CA Cancer J Clin 63(1):11–30. CrossRefPubMedGoogle Scholar
  3. 3.
    Shaikh T, Tam TY, Li T, Hayes SB, Goldstein L, Bleicher R, Boraas M, Sigurdson E, Ryan PD, Anderson P (2015) Multifocal and multicentric breast cancer is associated with increased local recurrence regardless of surgery type. Breast J Mar-Apr 21(2):121–126. CrossRefGoogle Scholar
  4. 4.
    Lu TP, Lee CY, Tsai MH, Chiu YC, Hsiao CK, Lai LC, Chuang EY (2012) miRSystem: an integrated system for characterizing enriched functions and pathways of microRNA targets. PLoS ONE 7(8):e42390. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Chiang CH, Hou MF, Hung WC (2013) Up-regulation of miR-182 by β-catenin in breast cancer increases tumorigenicity and invasiveness by targeting the matrix metalloproteinase inhibitor RECK. Biochim Biophys Acta 1830(4):3067–3076. CrossRefPubMedGoogle Scholar
  6. 6.
    Xue J, Zhou A, Wu Y, Morris SA, Lin K, Amin S, Verhaak R, Fuller G, Xie K, Heimberger AB, Huang S (2016) miR-182-5p induces by STAT-3 activation promotes glioma tumorigenesis. Cancer Res 76(14):4293–4304. CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Attema JL, Bert AG, Lim YY, Kolesnikoff N, Lawrence DM, Pillman KA, Smith E, Drew PA, Khew-Goodall Y, Shannon F, Goodall GJ (2013) Identification of an enhancer that increases miR-200b-200a-429 gen expression in breast cancer cells. PLoS ONE 8(9):e75517. CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Lv J, Xia K, Xu P, Sun E, Ma J, Gao S, Zhou Q, Zhang M, Wang F, Chen F, Zhou P, Fu Z, Xie H (2014) miRNA expression patterns in chemoresistant breast cancer tissues. Biomed Pharmacother 68(8):935–942. CrossRefPubMedGoogle Scholar
  9. 9.
    Hu M, Xia M, Chen X, Lin Z, Xu Y, Ma Y, Su L (2010) microRNA-141 regulates Smad Interacting Protein 1(SIP1) and inhibits migration and invasion of colorectal cancer cells. Dig Dis Sci 55(8):2365–2372. CrossRefPubMedGoogle Scholar
  10. 10.
    Zhang J, Kong X, Li J, Luo Q, Li X, Shen L, Chen L, Fang L (2014) miR-96 promotes tumor proliferation and invasion by targeting RECK in breast cancer. Oncol Rep 31(3):1357–1363. CrossRefPubMedGoogle Scholar
  11. 11.
    Guttilla IK, White BA (2009) Coordinate regulation of FOXO1 by miR-27a, miR-96, miR-182 in breast cancer. J Biol Chem 284(35):23204–23216. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Xu L, Zhong J, Guo B, Zhu Q, Liang H, Wen N, Yun W, Zhang L (2016) miR-96 promotes the growth of prostate carcinoma cells by suppressing MTSS1. Tumour Biol 37(9):12023–12032CrossRefPubMedGoogle Scholar
  13. 13.
    Liu T, Hu K, Zhao Z, Chen G, Ou X, Zhang H, Zhang X, Wei X, Wang D, Cui M, Liu C (2015) micro-RNA-1 down regulates proliferation and migration of breast cancer stem cells by inhibiting catenin pathway. Oncotarget 6(39):41638–41649. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Minemura H, Takagi K, Miki Y, Shibahara Y, Nakagawa S, Ebata A, Watanabe M, Ishida T, Sasano H, Suzuki T (2015) Abnormal expression of miR-1 in breast carcinoma as a potent prognostic factor. Cancer Sci 106(11):1642–1650. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Biagioni F, Bossel Ben-Moshe N, Fontemaggi G, Canu V, Mori F, Antoniani B, Di Benedetto A, Santoro R, Germoni S, De Angelis F, Cambria A, Avraham R, Grasso G, Strano S, Muti P, Mottolese M, Yarden Y, Domany E, Blandino G (2012) miR-10b, a master inhibitor of the cell cycle, is down regulated in human breast tumours. EMBO Mol Med 4(11):1214–1229. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Ma L, Reinhardt F, Pan E, Soutschek J, Bhat B, Marcusson EG, Teruya-Feldstein J, Bell GW, Weinberg RA (2010) Therapeutic silencing of miR-10b inhibits metastasis in a mouse mammary tumor model. Nat Biotechnol 28(4):341–347. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Ma L, Teruya-Feldstein J, Weinberg RA (2007) Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 449(7163):682–688CrossRefPubMedGoogle Scholar
  18. 18.
    Ahmad A, Ginnebaugh KR, Yin S, Bollig-Fischer A, Reddy KB, Sarkar FH (2015) Functional role of miR-10b in tamoxifen resistance of ER-positive breast cancer cells through down regulation of HDAC4. BMC Cancer 15:540. CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Qiu YH, Wei YP, Shen NJ, Wang ZC, Kan T, Yu WL, Yi B, Zhang YJ (2013) miR-204 inhibits epithelial to mesenchymal transition by targeting slug intrahepatic cholangiocarsinoma cells. Cell Physiol Biochem 32(5):1331–1341. CrossRefPubMedGoogle Scholar
  20. 20.
    Ying Z, Li Y, Wu J, Zhu X, Yang Y, Tian H, Li W, Hu B, Cheng SY, Li M (2013) Loss of miR-204 expression enhances glioma migration and stem cell-like phenotype. Cancer Res 73(2):990–999. CrossRefPubMedGoogle Scholar
  21. 21.
    Ryan J, Tivnan A, Fay J, Bryan K, Meehan M, Creevey L, Lynch J, Bray IM, O’Meara A, Tracey L, Davidoff AM, Stallings RL (2012) MicroRNA-204 increases sensitivity of neuroblastoma cells to cisplatin and is associated with a favourable clinical outcome. Br J Cancer 107(6):967–976. CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    Chung TK, Lau TS, Cheung TH, Yim SF, Lo KW, Siu NS, Chan LK, Yu MY, Kwong J, Doran G, Barroilhet LM, Ng AS, Wong RR, Wang VW, Mok SC, Smith DI, Berkowitz RS, Wong YF (2012) Dysregulation of microRNA-204 mediates migration and invasion of endometrial cancer by regulating FOXC1. Int J Cancer 130(5):1036–1045. CrossRefPubMedGoogle Scholar
  23. 23.
    Zhang L, Wang X, Chen P (2013) miR-204 down regulates SIRT1 and reverts SIRT1 induced epithelial to mesenchymal transition, anoikis resistance and invasion in gastric cancer. BMC Cancer 13:290. CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Imam JS, Plyler JR, Bansal H, Prajapati S, Bansal S, Rebeles J, Chen HI, Chang YF, Panneerdoss S, Zoghi B, Buddavarapu KC, Broaddus R, Hornsby P, Tomlinson G, Dome J, Vadlamudi RK, Pertsemlidis A, Chen Y, Rao MK (2012) Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization. PLoS ONE 7(12):e52397. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Ford HL, Kabingu EN, Bump EA, Mutter GL, Pardee AB (1998) Abrogation of the G2 cell cycle checkpoint assosiciated with overexpression of HSIX1: a possible mechanism of breast carcinogenesis. Proc Natl Acad Sci USA 95(21):12608–12613CrossRefPubMedGoogle Scholar
  26. 26.
    Zeng J, Wei M, Shi R, Cai C, Liu X, Li T, Ma W (2016) miR-204-5p/Six1 feedback loop promotes epithelial-mesenchimal transition in breast cancer. Tumour Biol 37(2):2729–2735. CrossRefPubMedGoogle Scholar
  27. 27.
    Li W, Jin X, Zhang Q, Zhang G, Deng X, Ma L (2014) Decreased expression of miR-204 is associated with poor prognosis in patients with breast cancer. Int J Clin Exp Pathol 7(6):3287–3292. eCollection 2014PubMedPubMedCentralGoogle Scholar
  28. 28.
    Kikkawa N, Hanazawa T, Fujimura L, Nohata N, Suzuki H, Chazono H, Sakurai D, Horiguchi S, Okamoto Y, Seki N (2010) miR-489 is a tumour suppressive miRNA target PTPN11 in hypofaryngeal squamos cell carcinoma. Br J Cancer 103(6):877–884. CrossRefPubMedPubMedCentralGoogle Scholar
  29. 29.
    Wu H, Xiao Z, Zhang H, Wang K, Liu W, Hao Q (2014) miR-489 modulates cisplatin resistance in human ovarian cancer cells by targetting Akt3. Anticancer Drugs 25(7):799–809. CrossRefPubMedGoogle Scholar
  30. 30.
    Jiang L, He D, Yang D, Chen Z, Pan Q, Mao A, Cai Y, Li X, Xing H, Shi M, Chen Y, Bruce IC, Wang T, Jin L, Qi X, Hua D, Jin J, Ma X (2014) miR-489 regulates chemoresistance in breast cancer via epithelial mesenchymal transition pathway. FEBS Lett 588(11):2009–2015. CrossRefPubMedGoogle Scholar
  31. 31.
    Fassan M, Baffa R, Palazzo JP, Lloyd J, Crosariol M, Liu CG, Volinia S, Alder H, Rugge M, Croce CM, Rosenberg (2009) A. MicroRNA expression profiling of male breast cancer. Breast Cancer Res 11(4):R58. CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Department of General SurgeryYerkoy State HospitalYozgatTurkey
  2. 2.Department of General Surgery, Medical FacultyBezmialem Vakif UniversityFatih/IstanbulTurkey
  3. 3.Department of Medical Biology, Faculty of MedicineUniversity of Health SciencesUskudar/IstanbulTurkey
  4. 4.Department of Pathology, Medical FacultyBezmialem Vakif UniversityIstanbulTurkey
  5. 5.Department of Radiology, Medical FacultyBezmialem Vakif UniversityIstanbulTurkey
  6. 6.Department of General Surgery, Medical FacultyIstanbul UniversityIstanbulTurkey

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