Skip to main content

Advertisement

SpringerLink
Log in

Identification and clinical implications of circulating microRNAs for estrogen receptor-positive breast cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

Cancer-associated microRNAs have been stably detected in blood. The objective of this study was to identify a panel of circulating microRNAs with the potential to serve as biomarkers for estrogen receptor-positive (ER+)/human epidermal growth factor receptor 2 (HER2)− breast cancer. We used microarray-based expression profiling to compare the levels of circulating microRNAs in blood samples from 11 ER+/HER2− advanced breast cancer patients plus 5 age-matched controls. MicroRNA levels were validated by reverse transcription quantitative polymerase chain reaction in 40 control subjects, 187 early breast cancer patients, and 45 metastatic breast cancer patients. Then, we assessed the association between the levels of microRNA and clinical outcomes of ER+/HER2− metastatic breast cancer. Initially, we found that miR-1280, miR-1260, and miR-720 were up-regulated in blood from breast cancer patients (P < 0.05). In validation, miR-1280 levels significantly increased in breast cancer patients and reflected tumor status (control<<early cancer<metastatic cancer). Among 37 metastatic breast cancer patients, miR-1280 levels significantly decreased after treatment in patients who responded to systemic treatment (P < 0.001). We confirmed that miR-1280 was not a classic microRNA, but a tRNALeu-derived fragment. These findings suggest that a circulating tRNA-derived microRNA, miR-1280, is differently expressed in breast cancer patients and may serve as a biomarker for ER-positive breast cancer.

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.

Institutional subscriptions

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

Similar content being viewed by others

Abbreviations

ER:

Estrogen receptor

HER2:

Human epidermal growth factor receptor 2

EBC:

Early breast cancer

MBC:

Metastatic breast cancer

PCR:

Polymerase chain reaction

qRT-PCR:

Quantitative reverse transcription PCR

DIG:

Digoxigenin

SD:

Standard deviation

RECIST:

Response Evaluation Criteria In Solid Tumors

OS:

Overall survival

RPA1:

Replication protein A1

References

  1. Esquela-Kerscher A, Slack FJ. Oncomirs—microRNAs with a role in cancer. Nat Rev Cancer. 2006;6(4):259–69.

    Article  CAS  Google Scholar 

  2. Calin GA, Croce CM. MicroRNA signatures in human cancers. Nat Rev Cancer. 2006;6(11):857–66.

    Article  CAS  Google Scholar 

  3. Iorio M, Ferracin M, Liu C-G, Veronese A, Spizzo R, Sabbioni S, et al. MicroRNA gene expression deregulation in human breast cancer. Cancer Res. 2005;65(16):7065–70.

    Article  CAS  Google Scholar 

  4. Lu J, Getz G, Miska EA, Alvarez-Saavedra E, Lamb J, Peck D, et al. MicroRNA expression profiles classify human cancers. Nature. 2005;435(7043):834–8.

    Article  CAS  Google Scholar 

  5. Garzon R, Calin G, Croce C. MicroRNAs in cancer. Annu Rev Med. 2009;60:167–79.

    Article  CAS  Google Scholar 

  6. Garzon R, Marcucci G, Croce C. Targeting microRNAs in cancer: rationale, strategies and challenges. Nat Rev Drug Discov. 2010;9(10):775–89.

    Article  CAS  Google Scholar 

  7. Kluiver J, Poppema S, de Jong D, Blokzijl T, Harms G, Jacobs S, et al. BIC and miR-155 are highly expressed in Hodgkin, primary mediastinal and diffuse large B cell lymphomas. J Pathol. 2005;207(2):243–9.

    Article  CAS  Google Scholar 

  8. Chan J, Krichevsky A, Kosik K. MicroRNA-21 is an antiapoptotic factor in human glioblastoma cells. Cancer Res. 2005;65(14):6029–33.

    Article  CAS  Google Scholar 

  9. Ventura A, Young A, Winslow M, Lintault L, Meissner A, Erkeland S, et al. Targeted deletion reveals essential and overlapping functions of the miR-17 through 92 family of miRNA clusters. Cell. 2008;132(5):875–86.

    Article  CAS  Google Scholar 

  10. Lowery A, Miller N, Devaney A, McNeill RE, Davoren PA, Lemetre C, et al. MicroRNA signatures predict oestrogen receptor, progesterone receptor and HER2/neu receptor status in breast cancer. Breast Cancer Res. 2009;11(3):R27.

    Article  Google Scholar 

  11. Blenkiron C, Goldstein L, Thorne N, Spiteri I, Chin S-F, Dunning M, et al. MicroRNA expression profiling of human breast cancer identifies new markers of tumor subtype. Genome Biol. 2007;8(10):R214.

    Article  Google Scholar 

  12. Lee DY, Deng Z, Wang CH, Yang BB. MicroRNA-378 promotes cell survival, tumor growth, and angiogenesis by targeting SuFu and Fus-1 expression. Proc Natl Acad Sci U S A. 2007;104(51):20350–5.

    Article  CAS  Google Scholar 

  13. Shimono Y, Zabala M, Cho R, Lobo N, Dalerba P, Qian D, et al. Downregulation of miRNA-200c links breast cancer stem cells with normal stem cells. Cell. 2009;138(3):592–603.

    Article  CAS  Google Scholar 

  14. Shenouda S, Alahari S. MicroRNA function in cancer: oncogene or a tumor suppressor? Cancer Metastasis Rev. 2009;28(3–4):369–78.

    Article  CAS  Google Scholar 

  15. Mitchell P, Parkin R, Kroh E, Fritz B, Wyman S, Pogosova-Agadjanyan E, et al. Circulating microRNAs as stable blood-based markers for cancer detection. Proc Natl Acad Sci U S A. 2008;105(30):10513–8.

    Article  CAS  Google Scholar 

  16. Heneghan H, Miller N, Lowery A. Circulating microRNAs as novel minimally invasive biomarkers for breast cancer. Ann Surg. 2010;251(3):499–505.

    Article  Google Scholar 

  17. Tsujiura M, Ichikawa D, Komatsu S, Shiozaki A, Takeshita H, Kosuga T, et al. Circulating microRNAs in plasma of patients with gastric cancers. Br J Cancer. 2010;102(7):1174–9.

    Article  CAS  Google Scholar 

  18. Wong T-S, Liu X-B, Wong B. Mature miR-184 as potential oncogenic microRNA of squamous cell carcinoma of tongue. Clin Cancer Res. 2008;14(9):2588–92.

    Article  CAS  Google Scholar 

  19. Hu Z, Chen X, Zhao Y, Tian T, Jin G, Shu Y, et al. Serum microRNA signatures identified in a genome-wide serum microRNA expression profiling predict survival of non-small-cell lung cancer. J Clin Oncol. 2010;28(10):1721–6.

    Article  Google Scholar 

  20. Sun Y, Wang M, Lin G, Sun S, Li X, Qi J, et al. Serum microRNA-155 as a potential biomarker to track disease in breast cancer. PLoS One. 2012;7(10):e47003.

    Article  CAS  Google Scholar 

  21. Zhao H, Shen J, Medico L, Wang D, Ambrosone C. A pilot study of circulating miRNAs as potential biomarkers of early stage breast cancer. PLoS One. 2010;5(10):e13735.

    Article  Google Scholar 

  22. Comparison of microRNA expression with whole blood between ER positive breast cancer patients and normal controls. http://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE53179.

  23. Schopman NC, Heynen S, Haasnoot J, Berkhout B. A miRNA-tRNA mix-up: tRNA origin of proposed miRNA. RNA Biol. 2010;7(5):573–6.

    Article  CAS  Google Scholar 

  24. Cheloufi S, Dos Santos C, Chong M, Hannon G. A dicer-independent miRNA biogenesis pathway that requires Ago catalysis. Nature. 2010;465(7298):584–9.

    Article  CAS  Google Scholar 

  25. Yang J, Lai E. Alternative miRNA biogenesis pathways and the interpretation of core miRNA pathway mutants. Mol Cell. 2011;43(6):892–903.

    Article  CAS  Google Scholar 

  26. Lee Y, Shibata Y, Malhotra A, Dutta A. A novel class of small RNAs: tRNA-derived RNA fragments (tRFs). Genes Dev. 2009;23(22):2639–49.

    Article  CAS  Google Scholar 

  27. Maute RL, Schneider C, Sumazin P, Holmes A, Califano A, Basso K, et al. tRNA-derived microRNA modulates proliferation and the DNA damage response and is down-regulated in B cell lymphoma. Proc Natl Acad Sci U S A. 2013;110(4):1404–9.

    Article  CAS  Google Scholar 

  28. Chan M, Liaw C, Ji S, Tan H, Wong C, Thike A, et al. Identification of circulating microRNA signatures for breast cancer detection. Clin Cancer Res. 2013;19(16):4477–87.

    Article  CAS  Google Scholar 

  29. Jung E-J, Santarpia L, Kim J, Esteva F, Moretti E, Buzdar A, et al. Plasma microRNA 210 levels correlate with sensitivity to trastuzumab and tumor presence in breast cancer patients. Cancer. 2012;118(10):2603–14.

    Article  CAS  Google Scholar 

Download references

Acknowledgments

This work was supported by NCC Grant 0910220 and NCC Grant 1110260.

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Center for Breast Cancer, National Cancer Center, Madu-dong, Ilsandong-gu, Goyangsi, South Korea

    In Hae Park, Joo Hyun Kang, Keun Seok Lee & Jungsil Ro

  2. Cancer Genomics Branch, National Cancer Center, Madu-dong, Ilsandong-gu, Goyangsi, South Korea

    Seungyoon Nam

  3. Yonsei Cancer Center, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemoon-gu, Seoul, 120-752, South Korea

    In Hae Park & Joo-Hang Kim

Authors
  1. In Hae Park
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Joo Hyun Kang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Keun Seok Lee
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Seungyoon Nam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Jungsil Ro
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Joo-Hang Kim
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Joo-Hang Kim.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Park, I.H., Kang, J.H., Lee, K.S. et al. Identification and clinical implications of circulating microRNAs for estrogen receptor-positive breast cancer. Tumor Biol. 35, 12173–12180 (2014). https://doi.org/10.1007/s13277-014-2525-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-2525-5

Keywords

Search

Navigation