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miR-153 inhibits epithelial–mesenchymal transition by targeting metadherin in human breast cancer

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Abstract

Epithelial–mesenchymal transition (EMT) is a crucial step in epithelial cancer invasion and metastasis. miR-153 has been identified as a key EMT suppressor. Accordingly, this study aimed to determine the possible relation of miR-153 downregulation to EMT through MTDH modulation. The miR-153 and MTDH expression profiles of human breast cancer specimen were determined by qPCR and evaluated by correlation analysis. Cell viability and clonogenic assays were applied to explore the impact of miR-153 on suppression of proliferation and oncogenic potential of breast cancer cells. Cell migration and invasion assays were used for the functional analysis of miR-153 in MCF-7 and MDA-MB-231 cells. Luciferase assay was adopted to identify MTDH as a new direct target of miR-153. Ectopic expression of miR-153 could significantly inhibit tumor growth and impair the migration and invasion of breast cancer cells. Overexpression of miR-153 simultaneously increased E-cadherin, decreased vimentin expression, and downmodulated EMT-associated transcription factors. miR-153 was negatively correlated with MTDH in cell lines and clinical samples. Overexpression of miR-153 significantly suppressed MTDH, as demonstrated by in vitro MTDH 3′-untranslated region luciferase report assay. MTDH is a direct downstream target of miR-153 and is involved in the miR-153-induced suppression of the migration and invasion of breast cancer cells. Our findings indicate that miR-153 functions as a tumor suppressor and miR-153/MTDH link is a promising therapeutic target for breast cancer.

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Acknowledgments

This study was supported by grants from National Nature Scientific Foundation of China (30901779, 81072068) and The Natural Science Foundation of Shandong Province (BS2011YY060, ZR2009CM047).

Conflict of interest

All authors of this paper have no financial and personal relationships with other people or organizations that could inappropriately influence this work.

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Authors and Affiliations

  1. Department of Pathology, Weifang Medical University, Weifang, 261053, Shandong Province, People’s Republic of China

    Wentong Li, Limin Zhai & Shijun Lv

  2. Department of Biology, Weifang Medical University, Weifang, 261053, Shandong Province, People’s Republic of China

    Chunling Zhao

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  1. Wentong Li
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  2. Limin Zhai
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  3. Chunling Zhao
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  4. Shijun Lv
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Correspondence to Wentong Li.

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Li, W., Zhai, L., Zhao, C. et al. miR-153 inhibits epithelial–mesenchymal transition by targeting metadherin in human breast cancer. Breast Cancer Res Treat 150, 501–509 (2015). https://doi.org/10.1007/s10549-015-3346-y

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  • DOI: https://doi.org/10.1007/s10549-015-3346-y

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