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

// Ruifen Dong 1 , Xiaolin Liu 1 , Qing Zhang 1 , Zhijun Jiang 1 , Yingwei Li 1 , Yuyan Wei 1 , Yinuo Li 1 , Qifeng Yang 4 , Jinsong Liu 6 , Jian-Jun Wei 5 , Changshun Shao 3 , Zhaojian Liu 2 , Beihua Kong 1 1 Department of Obstetrics and Gynecology, Qilu Hospital, Shandong University, Jinan, Shandong, China 2 Department 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 4 Department of Breast Surgery, Qilu Hospital, Shandong University, Jinan, Shandong, China 5 Department of Pathology, Northwestern University School of Medicine, Chicago, IL, USA 6 Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA Correspondence to: Beihua Kong, e-mail: kongbeihua@sdu.edu.cn Zhaojian Liu, e-mail: liujian9782@sdu.edu.cn 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.