Oncotarget

Research Papers:

miR-125a-5p is a prognostic biomarker that targets HDAC4 to suppress breast tumorigenesis

Tsung-Hua Hsieh _, Chia-Yi Hsu, Cheng-Fang Tsai, Cheng-Yu Long, Chee-Yin Chai, Ming-Feng Hou, Jau-Nan Lee, Deng-Chyang Wu, Shao-Chun Wang and Eing-Mei Tsai

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Oncotarget. 2015; 6:494-509. https://doi.org/10.18632/oncotarget.2674

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Abstract

Tsung-Hua Hsieh5, Chia-Yi Hsu1, Cheng-Fang Tsai1, Cheng-Yu Long5, Chee-Yin Chai3, Ming-Feng Hou4, Jau-Nan Lee5, Deng-Chyang Wu6, Shao-Chun Wang7, Eing-Mei Tsai1,2,5,6

1Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

2Center for Research Resources and Development, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

3Department of Pathology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

4Department of General Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

5Department of Obstetrics and Gynecology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

6Center for Stem Cell Research, Kaohsiung Medical University, Kaohsiung 80708, Taiwan

7Department of Cancer Biology, University of Cincinnati, College of Medicine, Cincinnati, Ohio 45267, USA

Correspondence to:

Eing-Mei Tsai, e-mail: tsaieing@yahoo.com

Keywords: miR-125a-5p, HDAC4, Tumorigenesis and breast cancer

Received: July 31, 2014     Accepted: November 02, 2014     Published: November 28, 2014

ABSTRACT

Identifying stably expressed tumor markers that can be used easily to detect cancer is currently an important area of cancer research. By using miRNA microarray, we identified 20 differentially expressed miRNAs in serum samples of breast cancer patients. Expression of miR-125a-5p was relatively lower in patients with shorter survival compared to long-term survivors. In a cohort of breast cancer patients (N = 300), serum expression of miR-125a-5p was negatively and significantly correlated with tumor grade (P = 0.004), lymph-node status (P = 0.004), and tumor size (P < 0.001). Low miR-125a-5p expression was an independent prognostic marker (OR = 0.421; 95% CI = 0.184 to 0.961; P = 0.04) associated with poor survival rates (P = 0.0062). We show that miR-125a-5p directly inhibits expression of the HDAC4 gene, resulting in tumor suppression in vitro and in vivo. Together these results demonstrate that serum miR-125a-5p level in breast cancer may be a useful prognostic biomarker and offer a novel therapeutic avenue by targeting HDAC4 in breast cancer.


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