Oncotarget

Research Papers:

microRNA-200c/141 upregulates SerpinB2 to promote breast cancer cell metastasis and reduce patient survival

Tiefeng Jin, Hoe Suk Kim, Sul Ki Choi, Eun Hye Hwang, Jisu Woo, Han Suk Ryu, Kwangsoo Kim, Aree Moon and Woo Kyung Moon _

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Oncotarget. 2017; 8:32769-32782. https://doi.org/10.18632/oncotarget.15680

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Abstract

Tiefeng Jin1,2,*, Hoe Suk Kim1,*, Sul Ki Choi1,3, Eun Hye Hwang1, Jisu Woo1, Han Suk Ryu4, Kwangsoo Kim5, Aree Moon6 and Woo Kyung Moon1,3

1Department of Radiology, Seoul National University Hospital, Jongno-gu, Seoul 03080, Korea

2Department of Pathology & Cancer Research Center, Yanbian University Medical College, Yanji 133002, China

3Department of Biomedical Science, Seoul National University College of Medicine, Seoul National University, Jongno-gu, Seoul 03080, Korea

4Department of Pathology, Seoul National University Hospital, Jongno-gu, Seoul 03080, Korea

5Division of Clinical Bioinformatics, Biomedical Research Institute, Seoul National University Hospital, Jongno-gu, Seoul 03080, Korea

6Duksung Innovative Drug Center College of Pharmacy, Duksung Women's University, Dobong-gu, Seoul 01369, Korea

*These authors have contributed equally to this work

Correspondence to:

Woo Kyung Moon, email: moonwk@snu.ac.kr

Keywords: SerpinB2, SerpinE1, metastasis, microRNA-200c/141, triple negative breast cancer

Received: June 06, 2016     Accepted: February 12, 2017     Published: February 24, 2017

ABSTRACT

The microRNA-200 (miR-200) family is associated with tumor metastasis and poor patient prognosis. We found that miR-200c/141 cluster overexpression upregulated SerpinB2 in the MDA-MB-231 triple-negative (TN) breast cancer cell line. We observed transcription factor (c-Jun, c-Fos, and FosB) upregulation, nuclear localization of c-Jun, and increased SerpinB2 promoter-directed chloramphenicol acetyltransferase activity in miR-200c/141 cluster-overexpressing cells relative to controls. Additionally, miR-124a and miR-26b, which directly target SepinB2, were downregulated compared to controls. In mouse xenograft models, miR-200c/141 cluster overexpression promoted lymph node and lung metastasis, and siRNA-mediated SerpinB2 knockdown decreased lung metastasis, suggesting that SerpinB2 mediates miR-200c/141-induced lung metastasis. We also explored the clinical significance of SerpinB2 protein status through analysis of primary breast tumor samples and The Cancer Genome Atlas (TCGA) data. High SerpinB2 levels were associated with reduced survival and increased lymph node metastasis in breast cancer patients. SerpinB2 was overexpressed in the TN breast cancer subtype as compared to the luminal subtype. The present study demonstrates that SerpinB2 promotes miR-200c/141 cluster overexpression-induced breast cancer cell metastasis, and SerpinB2 overexpression correlates with increased metastatic potential and unfavorable outcomes in breast cancer patients. SerpinB2 may be a useful biomarker for assessing metastasis risk in breast cancer patients.


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