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Tumor Biology

, Volume 36, Issue 1, pp 251–258 | Cite as

Identification of microRNA-93 as a functional dysregulated miRNA in triple-negative breast cancer

  • Jinhua Hu
  • Juan Xu
  • Yuquan Wu
  • Qingyong Chen
  • Wei Zheng
  • Xiaojun Lu
  • Chun Zhou
  • Demin Jiao
Research Article

Abstract

MicroRNAs (miRNAs) are widely recognized as key players in cancer progression and drug resistance, but less is known about the role of miRNAs in triple-negative (estrogen receptor, progesterone receptor, and HER-2/neu) breast cancer (TNBC). The aim of the present study was to examine the expression profile of miRNAs and to explore their possible roles in TNBC. Differentially expressed miRNAs were identified by miRNA microarray and verified by quantitative real-time polymerase chain reaction. The expression of miR-93 was assessed by in situ hybridization in 119 cases of breast cancer. Cell proliferation potential was examined by MTT assay. Cell migration and invasion abilities were evaluated by a wound healing assay and transwell invasion or migration assay. Seven upregulated and ten downregulated miRNAs in TNBC were identified. The miR-93 expression level in TNBC tissues was significantly higher than that in non-triple-negative breast cancer tissues. The potentials of proliferation, invasion, and metastasis in breast cancer MCF-7 cells were promoted by ectopic transfection of miR-93. Our study found several distinct differentially expressed miRNAs in TNBC, as compared to non-triple-negative breast cancer. Among them, miR-93 may be considered as a biomarker associated with the biological and clinical characteristics of human TNBC.

Keywords

Triple-negative breast cancer miR-93 In situ hybridization Cell proliferation Invasion and migration 

Notes

Acknowledgments

We thank Medjaden Bioscience Limited for assisting in the preparation of this manuscript.

Conflicts of interest

None

References

  1. 1.
    Bertheau P, Turpin E, Rickman DS, Espie M, de Reynies A, Feugeas JP, et al. Exquisite sensitivity of tp53 mutant and basal breast cancers to a dose-dense epirubicin-cyclophosphamide regimen. PLoS Med. 2007;4:e90.CrossRefPubMedPubMedCentralGoogle Scholar
  2. 2.
    Carey LA, Dees EC, Sawyer L, Gatti L, Moore DT, Collichio F, et al. The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res. 2007;13:2329–34.CrossRefPubMedGoogle Scholar
  3. 3.
    Nam BH, Kim SY, Han HS, Kwon Y, Lee KS, Kim TH, et al. Breast cancer subtypes and survival in patients with brain metastases. Breast Cancer Res. 2008;10:R20.CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Rakha EA, Reis-Filho JS, Ellis IO. Basal-like breast cancer: a critical review. J Clin Oncol. 2008;26:2568–81.CrossRefPubMedGoogle Scholar
  5. 5.
    Schneider BP, Winer EP, Foulkes WD, Garber J, Perou CM, Richardson A, et al. Triple-negative breast cancer: risk factors to potential targets. Clin Cancer Res. 2008;14:8010–8.CrossRefPubMedGoogle Scholar
  6. 6.
    Cho WC. OncomiRs: the discovery and progress of microRNAs in cancers. Mol Cancer. 2007;6:60.CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.CrossRefPubMedGoogle Scholar
  8. 8.
    Lee DY, Shatseva T, Jeyapalan Z, Du WW, Deng Z, Yang BB. A 3′-untranslated region (3′UTR) induces organ adhesion by regulating miR-199a* functions. PLoS One. 2009;4:e4527.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Jeyapalan Z, Deng Z, Shatseva T, Fang L, He C, Yang BB. Expression of cd44 3′-untranslated region regulates endogenous microRNA functions in tumorigenesis and angiogenesis. Nucleic Acids Res. 2011;39:3026–41.CrossRefPubMedGoogle Scholar
  10. 10.
    Fish JE, Santoro MM, Morton SU, Yu S, Yeh RF, Wythe JD, et al. Mir-126 regulates angiogenic signaling and vascular integrity. Dev Cell. 2008;15:272–84.CrossRefPubMedPubMedCentralGoogle Scholar
  11. 11.
    Wang S, Aurora AB, Johnson BA, Qi X, McAnally J, Hill JA, et al. The endothelial-specific microRNA miR-126 governs vascular integrity and angiogenesis. Dev Cell. 2008;15:261–71.CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Viticchie G, Lena AM, Latina A, Formosa A, Gregersen LH, Lund AH, et al. Mir-203 controls proliferation, migration and invasive potential of prostate cancer cell lines. Cell Cycle. 2011;10:1121–31.CrossRefPubMedGoogle Scholar
  13. 13.
    Shatseva T, Lee DY, Deng Z, Yang BB. MicroRNA miR-199a-3p regulates cell proliferation and survival by targeting caveolin-2. J Cell Sci. 2011;124:2826–36.CrossRefPubMedGoogle Scholar
  14. 14.
    Kahai S, Lee SC, Lee DY, Yang J, Li M, Wang CH, et al. MicroRNA miR-378 regulates nephronectin expression modulating osteoblast differentiation by targeting galnt-7. PLoS One. 2009;4:e7535.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Wang CH, Lee DY, Deng Z, Jeyapalan Z, Lee SC, Kahai S, et al. MicroRNA miR-328 regulates zonation morphogenesis by targeting cd44 expression. PLoS One. 2008;3:e2420.CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Shan SW, Lee DY, Deng Z, Shatseva T, Jeyapalan Z, Du WW, et al. MicroRNA miR-17 retards tissue growth and represses fibronectin expression. Nat Cell Biol. 2009;11:1031–8.CrossRefPubMedGoogle Scholar
  17. 17.
    Nohata N, Hanazawa T, Enokida H, Seki N. MicroRNA-1/133a and microRNA-206/133b clusters: dysregulation and functional roles in human cancers. Oncotarget. 2012;3:9–21.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Fang L, Deng Z, Shatseva T, Yang J, Peng C, Du WW, et al. MicroRNA miR-93 promotes tumor growth and angiogenesis by targeting integrin-beta8. Oncogene. 2011;30:806–21.CrossRefPubMedGoogle Scholar
  19. 19.
    Luo L, Ye G, Nadeem L, Fu G, Yang BB, Honarparvar E, et al. MicroRNA-378a-5p promotes trophoblast cell survival, migration and invasion by targeting nodal. J Cell Sci. 2012;125:3124–32.CrossRefPubMedGoogle Scholar
  20. 20.
    Ma L, Teruya-Feldstein J, Weinberg RA. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.CrossRefPubMedGoogle Scholar
  21. 21.
    Huang Q, Gumireddy K, Schrier M, le Sage C, Nagel R, Nair S, et al. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat Cell Biol. 2008;10:202–10.CrossRefPubMedGoogle Scholar
  22. 22.
    Drakaki A, Iliopoulos D. MicroRNA gene networks in oncogenesis. Curr Genomics. 2009;10:35–41.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Stenvang J, Silahtaroglu AN, Lindow M, Elmen J, Kauppinen S. The utility of LNA in microRNA-based cancer diagnostics and therapeutics. Semin Cancer Biol. 2008;18:89–102.CrossRefPubMedGoogle Scholar
  24. 24.
    Esquela-Kerscher A, Slack FJ. OncomiRs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6:259–69.CrossRefPubMedGoogle Scholar
  25. 25.
    Zhang W, Dahlberg JE, Tam W. MicroRNAs in tumorigenesis: a primer. Am J Pathol. 2007;171:728–38.CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Gumireddy K, Li A, Gimotty PA, Klein-Szanto AJ, Showe LC, Katsaros D, et al. Klf17 is a negative regulator of epithelial-mesenchymal transition and metastasis in breast cancer. Nat Cell Biol. 2009;11:1297–304.CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Johnson CD, Esquela-Kerscher A, Stefani G, Byrom M, Kelnar K, Ovcharenko D, et al. The let-7 microRNA represses cell proliferation pathways in human cells. Cancer Res. 2007;67:7713–22.CrossRefPubMedGoogle Scholar
  28. 28.
    Shi L, Cheng Z, Zhang J, Li R, Zhao P, Fu Z, et al. Hsa-miR-181a and hsa-miR-181b function as tumor suppressors in human glioma cells. Brain Res. 2008;1236:185–93.CrossRefPubMedGoogle Scholar
  29. 29.
    Li Y, Tan W, Neo TW, Aung MO, Wasser S, Lim SG, et al. Role of the miR-106b-25 microRNA cluster in hepatocellular carcinoma. Cancer Sci. 2009;100:1234–42.CrossRefPubMedGoogle Scholar
  30. 30.
    Matsubara H, Takeuchi T, Nishikawa E, Yanagisawa K, Hayashita Y, Ebi H, et al. Apoptosis induction by antisense oligonucleotides against miR-17-5p and miR-20a in lung cancers overexpressing miR-17-92. Oncogene. 2007;26:6099–105.CrossRefPubMedGoogle Scholar
  31. 31.
    Mu P, Han YC, Betel D, Yao E, Squatrito M, Ogrodowski P, et al. Genetic dissection of the miR-17~92 cluster of microRNAs in Myc-induced b-cell lymphomas. Genes Dev. 2009;23:2806–11.CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Visser S, Yang X. LATS tumor suppressor: a new governor of cellular homeostasis. Cell Cycle. 2010;9:3892–903.CrossRefPubMedGoogle Scholar
  33. 33.
    Fang L, Du WW, Yang W, Rutnam ZJ, Peng C, Li H, et al. MiR-93 enhances angiogenesis and metastasis by targeting LATS2. Cell Cycle. 2012;11:4352–65.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Liu S, Patel SH, Ginestier C, Ibarra I, Martin-Trevino R, Bai S, et al. MicroRNA93 regulates proliferation and differentiation of normal and malignant breast stem cells. PLoS Genet. 2012;8:e1002751.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2014

Authors and Affiliations

  • Jinhua Hu
    • 1
  • Juan Xu
    • 1
  • Yuquan Wu
    • 1
  • Qingyong Chen
    • 2
  • Wei Zheng
    • 1
  • Xiaojun Lu
    • 1
  • Chun Zhou
    • 1
  • Demin Jiao
    • 2
  1. 1.Department of Geriatricsthe 117th Hospital of PLAHangzhouChina
  2. 2.Department of Respirationthe 117th Hospital of PLAHangzhouChina

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