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MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer

  • Preclinical Study
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Breast Cancer Research and Treatment Aims and scope Submit manuscript

Abstract

Tumor recurrence and metastasis result in an unfavorable prognosis for cancer patients. Recent studies have suggested that specific microRNAs (miRNAs) may play important roles in the development of cancer cells. However, prognostic markers and the outcome prediction of the miRNA signature in breast cancer patients have not been comprehensively assessed. The aim of this study was to identify miRNA biomarkers relating to clinicopathological features and outcome of breast cancer. A miRNA microarray analysis was performed on breast tumors of different lymph node metastasis status and with different progression signatures, indicated by overexpression of cyclin D1 and β-catenin genes, to identify miRNAs showing a significant difference in expression. The functional interaction between the candidate miRNA, miR-30a, and the target gene, Vim, which codes for vimentin, a protein involved in epithelial–mesenchymal transition, was examined using the luciferase reporter assay, western blotting, and migration and invasion assays. The association between the decreased miR-30a levels and breast cancer progression was examined in a survival analysis. miR-30a negatively regulated vimentin expression by binding to the 3′-untranslated region of Vim. Overexpression of miR-30a suppressed the migration and invasiveness phenotypes of breast cancer cell lines. Moreover, reduced tumor expression of miR-30a in breast cancer patients was associated with an unfavorable outcome, including late tumor stage, lymph node metastasis, and worse progression (mortality and recurrence) (p < 0.05). In conclusion, these findings suggest a role for miR-30a in inhibiting breast tumor invasiveness and metastasis. The finding that miR-30a downmodulates vimentin expression might provide a therapeutic target for the treatment of breast cancer.

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Abbreviations

IDC:

Invasive ductal carcinoma

EMT:

Epithelial–mesenchymal transition

miRNA:

microRNA

3′UTR:

3′-untranslated region

LNM:

Lymph node metastasis

LCM:

Laser capture microdissection

qRT-PCR:

Quantitative real-time reverse transcription polymerase chain reaction

DFS:

Disease-free survival

OS:

Overall survival

HR:

Hazard ratio

OR:

Odds ratio

95 % CI:

95 % confidence interval

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Acknowledgments

We sincerely appreciate Ms. Show-Lin Yang for her assistance in organizing our study specimens. This study was supported by research grant NSC 98-2314-B-040-009-MY3 from the National Science Council, Taipei, Taiwan.

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, Taichung, 40201, Taiwan

    Chun-Wen Cheng, Chia-Wei Chang & Cheng-You Chen

  2. Clinical Laboratory, Chung Shan Medical University Hospital, Taichung, Taiwan

    Chun-Wen Cheng

  3. Institute of Biomedical Sciences, Academia Sinica, Taipei, 11529, Taiwan

    Chun-Wen Cheng, Hsiao-Wei Wang, Hou-Wei Chu & Chen-Yang Shen

  4. Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

    Jyh-Cherng Yu

  5. Department of Biological Science and Technology, National Chiao Tung University, Hsinchu, Taiwan

    Jui-I Chao & Huei-Fang Liu

  6. Department of Nursing, Kang-Ning Junior College of Medical Care and Management, Taipei, Taiwan

    Shian-ling Ding

  7. Graduate Institute of Environmental Science, China Medical University, Taichung, Taiwan

    Chen-Yang Shen

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  1. Chun-Wen Cheng
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  2. Hsiao-Wei Wang
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Correspondence to Chun-Wen Cheng or Chen-Yang Shen.

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Cheng, CW., Wang, HW., Chang, CW. et al. MicroRNA-30a inhibits cell migration and invasion by downregulating vimentin expression and is a potential prognostic marker in breast cancer. Breast Cancer Res Treat 134, 1081–1093 (2012). https://doi.org/10.1007/s10549-012-2034-4

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  • DOI: https://doi.org/10.1007/s10549-012-2034-4

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