Breast Cancer Research and Treatment

, Volume 147, Issue 1, pp 39–49 | Cite as

MicroRNA-9 is associated with epithelial-mesenchymal transition, breast cancer stem cell phenotype, and tumor progression in breast cancer

  • Jae Moon Gwak
  • Hyun Jeong Kim
  • Eun Joo Kim
  • Yul Ri Chung
  • Sumi Yun
  • An Na Seo
  • Hee Jin Lee
  • So Yeon Park
Preclinical study

Abstract

MicroRNAs (miRNAs) are involved in the progression of breast cancer. Some miRNAs, especially the miR-200 family, miR-9, and miR-155 have been reported to be associated with epithelial-mesenchymal transition (EMT) and breast cancer stem cell (BCSC) phenotypes. This study was designed to evaluate the expression levels of these miRNAs in human breast cancer samples and analyzed their relationship with clinicopathologic features of the tumor including breast cancer subtype, EMT, BCSC phenotype, and prognosis. Expression levels of the miR-200 family, miR-9, and miR-155 were quantified using qRT-PCR. Breast cancer subtype, BCSC phenotype (CD44+/CD24− and ALDH1+), and expression of EMT markers (vimentin expression and E-cadherin loss) were evaluated by immunohistochemistry. miR-9 was more highly expressed in HER2+ and triple-negative subtypes than in luminal subtypes. Its expression level was significantly higher in tumors with high T stage, high histologic grade, p53 overexpression, and high proliferation index. Expression of miR-9 was also higher in tumors showing the CD44+/CD24− phenotype, vimentin expression, and E-cadherin loss. Furthermore, high level of miR-9 expression was found to be an independent prognostic factor for poor disease-free survival of the patients. Expression of miR-200a and miR-141 was highest in luminal A subtype, and miR-155 expression was highest in triple-negative subtype. Although the expression levels of some miR-200 family members and miR-155 showed difference with regard to EMT or BCSC phenotype, they were not associated with patients’ prognosis. In conclusion, overexpression of miR-9 is found in tumors with aggressive phenotypes and is associated with poor prognosis in breast cancer, suggesting that it may serve as a potential biomarker for breast cancer progression and a target for treatment.

Keywords

Breast cancer miR-9 Epithelial-mesenchymal transition Breast cancer stem cell Progression 

Notes

Acknowledgments

This study was supported by a Grant from Seoul National University Bundang Hospital and SK telecom, Republic of Korea (06-2013-095) to Park SY.

Conflict of interest

All authors declare no conflict of interests.

Supplementary material

10549_2014_3069_MOESM1_ESM.doc (160 kb)
Supplementary material 1 (DOC 160 kb)
10549_2014_3069_MOESM2_ESM.doc (37 kb)
Supplementary material 2 (DOC 37 kb)
10549_2014_3069_MOESM3_ESM.doc (86 kb)
Supplementary material 3 (DOC 85 kb)

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Jae Moon Gwak
    • 1
  • Hyun Jeong Kim
    • 2
  • Eun Joo Kim
    • 2
  • Yul Ri Chung
    • 1
  • Sumi Yun
    • 1
  • An Na Seo
    • 2
  • Hee Jin Lee
    • 3
  • So Yeon Park
    • 1
    • 2
  1. 1.Department of PathologySeoul National University College of MedicineSeoulRepublic of Korea
  2. 2.Department of PathologySeoul National University Bundang HospitalSeongnam-SiRepublic of Korea
  3. 3.Department of Pathology, Asan Medical CenterUniversity of Ulsan College of MedicineSeoulRepublic of Korea

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