Oncotarget

Research Papers:

miR-145 inhibits tumor growth and metastasis by targeting metadherin in high-grade serous ovarian carcinoma

Ruifen Dong _, Xiaolin Liu, Qing Zhang, Zhijun Jiang, Yingwei Li, Yuyan Wei, Yinuo Li, Qifeng Yang, Jinsong Liu, Jian-Jun Wei, Changshun Shao, Zhaojian Liu and Beihua Kong

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Oncotarget. 2014; 5:10816-10829. https://doi.org/10.18632/oncotarget.2522

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Abstract

Ruifen Dong1, Xiaolin Liu1, Qing Zhang1, Zhijun Jiang1, Yingwei Li1, Yuyan Wei1, Yinuo Li1, Qifeng Yang4, Jinsong Liu6, Jian-Jun Wei5, Changshun Shao3, Zhaojian Liu2, Beihua Kong1

1Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China

2Department of Cell Biology, Shandong University School of Medicine, Jinan, Shandong, China

3 Ministry of Education Key Laboratory of Experimental Teratology and Department of Molecular Medicine and Genetics, Shandong University School of Medicine, Jinan, China

4Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China

5Department of Pathology, Northwestern University School of Medicine, Chicago, IL, USA

6Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

Correspondence to:

Beihua Kong, e-mail: [email protected]

Zhaojian Liu, e-mail: [email protected]

Keywords: miR-145, MTDH, p53, HGSOC, metastasis

Received: September 18, 2014     Accepted: September 25, 2014     Published: October 14, 2014

ABSTRACT

High-grade serous ovarian carcinoma (HGSOC), the most common and aggressive subtype of epithelial ovarian cancer, is characterized by TP53 mutations and genetic instability. Using miRNA profiling analysis, we found that miR-145, a p53 regulated miRNA, was frequently down-regulated in HGSOC. miR-145 down-regulation was further validated in a large cohort of HGSOCs by qPCR. Overexpression of miR-145 in ovarian cancer cells significantly suppressed proliferation, migration and invasion in vitro and inhibited tumor growth and metastasis in vivo. Metadherin (MTDH) was subsequently identified as a direct target of miR-145, and was found to be significantly up-regulated in HGSOC. Furthermore, overexpression of MTDH rescued the inhibitory effects of miR-145 in ovarian cancer cells. Finally, we found that high level of MTDH expression correlated with poor prognosis of HGSOC. Therefore, lack of suppression of MTDH by miR-145 when p53 is dysfunctional leads to increased tumor growth and metastasis of HGSOC. Our study established a new link between p53, miR-145 and MTDH in the regulation of tumor growth and metastasis in HGSOC.


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