Skip to main content
SpringerLink
Log in

Breast Cancer MicroRNAs: Clinical Biomarkers for the Diagnosis and Treatment Strategies

  • Chapter
  • First Online:
Omics Approaches in Breast Cancer

Abstract

Breast cancer is the second most common cancer in females that accounts for the highest cancer-specific deaths worldwide. Although recent advances in clinical management significantly reduced the mortality rate in breast cancer patients, the success rate of the effective therapy remains largely dependent on early detection. It has been demonstrated that gene expression profile may be a useful tool to define the signature of breast cancer as well as to predict the prognosis or response to treatment. The microRNA expression profile is gaining lots of attention to define various types of cancers since they play critical roles in many different cellular processes including metabolism, apoptosis, differentiation, and development. Several studies have shown that microRNA’s signatures are associated with the staging, progression, and response to treatment in breast cancer. In addition to this microRNA has been shown to act as oncogenes and tumor suppressor genes.

Continued efforts to delineate the microRNA function in mammary physiological and pathological conditions will reveal novel insights into normal cells and breast cancer biology and ultimately provide a new molecular target for alternate therapy. The book chapter covers the role of microRNAs in the diagnosis, staging, progression, prognosis, and response to treatment of breast cancer.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 59.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Filipowicz W, Bhattacharyya SN, Sonenberg N. Mechanisms of post-transcriptional regulation by microRNAs: are the answers in sight? Nat Rev Genet. 2008;9:102–14.

    Article  PubMed  CAS  Google Scholar 

  2. Bartel DP. MicroRNAs: genomics, biogenesis, mechanism, and function. Cell. 2004;116:281–97.

    Article  PubMed  CAS  Google Scholar 

  3. Ambros V. The functions of animal microRNAs. Nature. 2004;431:350–5.

    Article  PubMed  CAS  Google Scholar 

  4. Malumbres M. miRNAs versus oncogenes: the power of social networking. Mol Syst Biol. 2012;8:569. doi:10.1038/msb.2012.2.

    Article  PubMed  PubMed Central  Google Scholar 

  5. Cai CK, Zhao GY, Tian LY, Yan K, Ma YL, Ji ZW, et al. miR-15a and miR-16-1 downregulate CCND1 and induce apoptosis and cell cycle arrest in osteosarcoma. Oncol Rep. 2012;28:1764–70.

    PubMed  CAS  Google Scholar 

  6. Yan K, Gao J, Yang T. MicroRNA-34a inhibits the proliferation and metastasis of osteosarcoma cells both in vitro and in vivo. PLoS One. 2012;7(3):e33778.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  7. American Cancer Society. Global cancer facts & figures. http://www.cancer.org (2011). Accessed 2012.

  8. Lee RC, Feinbaum RL, Ambros V. The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell. 1993;75(5):843–54.

    Article  PubMed  CAS  Google Scholar 

  9. Wightman B, Ha I, Ruvkun G. Posttranscriptional regulation of the heterochronic gene lin-14 by lin-4 mediates temporal pattern formation in C. elegans. Cell. 1993;75(5):855–62.

    Article  PubMed  CAS  Google Scholar 

  10. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, et al. The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature. 2000;403(6772):901–6.

    Article  PubMed  CAS  Google Scholar 

  11. Krek A, Grün D, Poy MN, Wolf R, Rosenberg L, Epstein EJ, et al. Combinatorial microRNA target predictions. Nat Genet. 2005;37(5):495–500.

    Article  PubMed  CAS  Google Scholar 

  12. Faller M, Guo F. MicroRNA biogenesis: there’s more than one way to skin a cat. Biochim Biophys Acta. 2008;1779(11):663–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  13. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T. Identification of novel genes coding for small expressed RNAs. Science. 2001;294:853–8.

    Article  PubMed  CAS  Google Scholar 

  14. Lau NC, Lim LP, Weinstein EG, Bartel DP. An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science. 2001;294:858–62.

    Article  PubMed  CAS  Google Scholar 

  15. Lee Y, Jeon K, Lee JT, Kim S, Kim VN. MicroRNA maturation: stepwise processing and subcellular localization. EMBO J. 2002;21:4663–70.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  16. Rodriguez A, Griffiths-Jones S, Ashurst JL, Bradley A. Identification of mammalian microRNA host genes and transcription units. Genome Res. 2004;14(10A):1902–10.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  17. Lee Y, Kim M, Han J, Yeom KH, Lee S, Baek SH, Kim VN. MicroRNA genes are transcribed by RNA polymerase II. EMBO J. 2004;23(20):4051–60.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  18. Borchert GM, Lanier W, Davidson BL. RNA polymerase III transcribes human microRNAs. Nat Struct Mol Biol. 2006;13(12):1097–101.

    Article  PubMed  CAS  Google Scholar 

  19. Kim VN. MicroRNA biogenesis: coordinated cropping and dicing. Nat Rev Mol Cell Biol. 2005;6:376.

    Article  PubMed  CAS  Google Scholar 

  20. Baskerville S, Bartel DP. Microarray profiling of microRNAs reveals frequent coexpression with neighboring miRNAs and host genes. RNA. 2005;11(3):241–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  21. Miska EA. How microRNAs control cell division, differentiation and death. Curr Opin Genet Dev. 2005;15:563–8.

    Article  PubMed  CAS  Google Scholar 

  22. Volinia S, Calin GA, Liu CG, Ambs S, Cimmino A, Petrocca F, et al. A microRNA expression signature of human solid tumors defines cancer gene targets. Proc Natl Acad Sci U S A. 2006;103:2257–61.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  23. Zhang B, Pan X, Cobb GP, Anderson TA. microRNAs as oncogenes and tumor suppressors. Dev Biol. 2007;302:1–12.

    Article  PubMed  CAS  Google Scholar 

  24. Hernando E. microRNAs and cancer: role in tumorigenesis, patient classification and therapy. Clin Transl Oncol. 2007;9:155–60.

    Article  PubMed  CAS  Google Scholar 

  25. Jiang J, Lee EJ, Gusev Y, Schmittgen TD. Real-time expression profiling of microRNA precursors in human cancer cell lines. Nucleic Acids Res. 2005;33:5394–403.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  26. Wark AW, Lee HJ, Corn RM. Multiplexed detection methods for profiling microRNA expression in biological samples. Angew Chem Int Ed Engl. 2008;47:644–52.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Nelson PT, Baldwin DA, Scearce LM, Oberholtzer JC, Tobias JW, Mourelatos Z. Microarray-based, high-throughput gene expression profiling of microRNAs. Nat Methods. 2004;1:155–61.

    Article  PubMed  CAS  Google Scholar 

  28. Chen C, Ridzon DA, Broomer AJ, Zhou Z, Lee DH, Nguyen JT, et al. Real-time quantification of microRNAs by stem-loop RT–PCR. Nucleic Acids Res. 2005;33:e179.

    Article  PubMed  PubMed Central  Google Scholar 

  29. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435:834–8.

    Article  PubMed  CAS  Google Scholar 

  30. Hafner M, Landgraf P, Ludwig J, Rice A, Ojo T, Lin C, et al. Identification of microRNAs and other small regulatory RNAs using cDNA library sequencing. Methods. 2008;44:3–12.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  31. Silveri L, Tilly G, Vilotte JL, Le Provost F. MicroRNA involvement in mammary gland development and breast cancer. Reprod Nutr Dev. 2006;46:549–56.

    Article  PubMed  CAS  Google Scholar 

  32. Iorio MV, Ferracin M, Liu CG, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65:7065–70.

    Article  PubMed  CAS  Google Scholar 

  33. Mattie MD, Benz CC, Bowers J, Sensinger K, Wong L, Scott GK, et al. Optimized high-throughput microRNA expression profiling provides novel biomarker assessment of clinical prostate and breast cancer biopsies. Mol Cancer. 2006;5:24.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Si ML, Zhu S, Wu H, Lu Z, Wu F, Mo YY. miR-21-mediated tumor growth. Oncogene. 2007;26:2799–803.

    Article  PubMed  CAS  Google Scholar 

  35. Shi W, Gerster K, Alajez N, Tsang J, Waldron L, Pintilie M, et al. Effect of the novel oncomir MiR-301 on tumor proliferation and invasion in human breast cancer. J Clin Oncol. 2010 (Suppl 28):15s (abstr 1076).

    Google Scholar 

  36. Rao X, Di Leva G, Li M, Fang F, Devlin C, Hartman-Frey C, et al. MicroRNA-221/222 confers breast cancer fulvestrant resistance by regulating multiple signaling pathways. Oncogene. 2011;30(9):1082–97. doi:10.1038/onc.2010.487.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  37. Radojicic J, Zaravinos A, Vrekoussis T, Kafousi M, Spandidos DA, Stathopoulos EN. MicroRNA expression analysis in triple-negative (ER, PR and Her2/neu) breast cancer. Cell Cycle. 2011;10(3):507–17. Epub 2011 Feb 1.

    Article  PubMed  CAS  Google Scholar 

  38. Imam JS, Plyler JR, Bansal H, Prajapati S, Bansal S, Rebeles J, et al. Genomic loss of tumor suppressor miRNA-204 promotes cancer cell migration and invasion by activating AKT/mTOR/Rac1 signaling and actin reorganization. PLoS One. 2012;7(12):e52397. doi:10.1371/journal.pone.0052397.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  39. Lee YM, Lee JY, Ho CC, Hong QS, Yu SL, Tzeng CR, et al. miRNA-34b as a tumor suppressor in estrogen-dependent growth of breast cancer cells. Breast Cancer Res. 2011;13(6):R116. doi:10.1186/bcr3059. Epub 2011 Nov 23.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  40. Massimo N, Calin GA. Breast cancer metastasis: a microRNA story. Breast Cancer Res. 2008;10:303.

    Google Scholar 

  41. Moriarty CH, Pursell B, Mercurio AM. miR-10b targets Tiam1: implications for Rac activation and carcinoma migration. J Biol Chem. 2010;285:20541–6.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  42. Ma L, Teruya-Feldstein J, Weinberg RA. Tumor invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449:682–8.

    Article  PubMed  CAS  Google Scholar 

  43. 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.

    Article  PubMed  CAS  Google Scholar 

  44. Tavazoie SF, Alarcon C, Oskarsson T, Padua D, Wang Q, Bos PD, et al. Endogenous human microRNAs that suppress breast cancer metastasis. Nature. 2008;451:147–52.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  45. Baranwal S, Alahari SK. Molecular mechanisms controlling E-cadherin expression in breast cancer. Biochem Biophys Res Commun. 2009;384:6–11.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  46. Hurteau GJ, Carlson JA, Roos E, Brock CJ. Stable expression of miR-200c alone is sufficient to regulate TCF8 (ZEB1) and restore E-cadherin expression. Cell Cycle. 2009;8:2064–9.

    Article  PubMed  CAS  Google Scholar 

  47. Gregory PA, Bert AG, Paterson EL, Barry SC, Tsykin A, Farshid G, et al. The miR-200 family and miR-205 regulate epithelial to mesenchymal transition by targeting ZEB1 and SIP1. Nat Cell Biol. 2008;10:593–601.

    Article  PubMed  CAS  Google Scholar 

  48. Korpal M, Lee ES, Hu G, Kang Y. The miR-200 family inhibits epithelial-mesenchymal transition and cancer cell migration by direct targeting of E-cadherin transcriptional repressors ZEB1 and ZEB2. J Biol Chem. 2008;283:14910–4.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  49. Park SM, Gaur AB, Lengyel E, Peter ME. The miR-200 family determines the epithelial phenotype of cancer cells by targeting the E-cadherin repressors ZEB1 and ZEB2. Genes Dev. 2008;22:894–907.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  50. Tryndyak VP, Beland FA, Pogribny IP. E-cadherin transcriptional down-regulation by epigenetic and microRNA-200 family alterations is related to mesenchymal and drug-resistant phenotypes in human breast cancer cells. Int J Cancer. 2010;126:2575–83.

    PubMed  CAS  Google Scholar 

  51. Valastyan S, Benaich N, Chang A, Reinhardt F, Weinberg RA. Concomitant suppression of three target genes can explain the impact of a microRNA on metastasis. Genes Dev. 2009;23:2592–7.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  52. Salter KH, Acharya CR, Walters KS, Redman R, Angulano A, Garman KS, et al. An integrated approach to the prediction of chemotherapeutic response in patients with breast cancer. PLoS One. 2008;3(4):e1908.

    Article  PubMed  PubMed Central  Google Scholar 

  53. Mishra PJ, Humeniuk R, Mishra PJ, Longo-Sorbello GS, Banerjee D, Bertino JR. A miR-24 microRNA binding-site polymorphism in dihydrofolate reductase gene leads to methotrexate resistance. Proc Natl Acad Sci U S A. 2007;104(33):13513–8. Epub 2007 Aug 8.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  54. Scott GK, Mattie MD, Berger CE, Benz SC, Benz CC. Rapid alteration of microRNA levels by histone deacetylase inhibition. Cancer Res. 2006;66(3):1277–81.

    Article  PubMed  CAS  Google Scholar 

  55. Saito Y, Liang G, Egger G, Friedman JM, Chuang JC, Coetzee GA, et al. Specific activation of microRNA-127 with downregulation of the proto-oncogene BCL6 by chromatin-modifying drugs in human cancer cells. Cancer Cell. 2006;9:435–43.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Medicine, Karolinska University Hospital, Karolinska Institute, Stockholm, Sweden

    Gowhar Shafi PhD, Ananta Paine PhD & Jesper Tegner PhD

  2. Department of Biotechnology, R & D Center, Bharathiar University, Coimbatore, Tamil Nadu, India

    Tarique N. Hasan MSc & Naveed Ahmed Syed MSc

  3. Department of Molecular Biology, Centre for Human Genetics, School of Health Sciences, Central University of Punjab, Bathinda, Punjab, India

    Anjana Munshi PhD

Authors
  1. Gowhar Shafi PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Tarique N. Hasan MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Naveed Ahmed Syed MSc
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ananta Paine PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jesper Tegner PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Anjana Munshi PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Gowhar Shafi PhD .

Editor information

Editors and Affiliations

  1. Institute of Integrative Omics, West Bengal, West Bengal, India

    Debmalya Barh

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer India

About this chapter

Cite this chapter

Shafi, G., Hasan, T.N., Syed, N.A., Paine, A., Tegner, J., Munshi, A. (2014). Breast Cancer MicroRNAs: Clinical Biomarkers for the Diagnosis and Treatment Strategies. In: Barh, D. (eds) Omics Approaches in Breast Cancer. Springer, New Delhi. https://doi.org/10.1007/978-81-322-0843-3_8

Download citation

  • DOI: https://doi.org/10.1007/978-81-322-0843-3_8

  • Published:

  • Publisher Name: Springer, New Delhi

  • Print ISBN: 978-81-322-0842-6

  • Online ISBN: 978-81-322-0843-3

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation