MicroRNA-320a inhibits breast cancer metastasis by targeting metadherin
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Juan Yu1,*, Ji-Gang Wang1,2,*, Lei Zhang1, Hai-Ping Yang3, Lei Wang1, Di Ding1, Qi Chen1, Wen-Lin Yang1, Ke-Han Ren1, Dan-Mei Zhou1, Qiang Zou4, Yi-Ting Jin4, Xiu-Ping Liu1,5
1Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China
2Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China
3Department of Pathology, People’s Hospital, Linzi District, Zibo 255400, China
4Department of Breast Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China
5Department of Pathology, The Fifth People’s Hospital, Fudan University, Shanghai 200240, China
*These authors contributed equally to this work and are co-first authors
Xiu-Ping Liu, email: [email protected]
Yi-Ting Jin, email: [email protected]
Keywords: miR-320a, MTDH, metastasis, breast cancer
Received: September 05, 2015 Accepted: May 01, 2016 Published: May 24, 2016
Dysregulated microRNAs play important pathological roles in carcinogenesis that are yet to be fully elucidated. This study was performed to investigate the biological functions of microRNA-320a (miR-320a) in breast cancer and the underlying mechanisms. Function analyses for cell proliferation, cell cycle, and cell invasion/migration, were conducted after miR-320a silencing and overexpression. The specific target genes of miR-320a were predicted by TargetScan algorithm and then determined by dual luciferase reporter assay and rescue experiment. The relationship between miR-320a and its target genes was explored in human breast cancer tissues. We found that miR-320a overexpression could inhibit breast cancer invasion and migration abilities in vitro, while miR-320a silencing could enhance that. In addition, miR-320a could suppress activity of 3′-untranslated region luciferase of metadherin (MTDH), a potent oncogene. The rescue experiment revealed that MTDH was a functional target of miR-320a. Moreover, we found that MTDH was negatively correlated with miR-320a expression, and it was related to clinical outcomes of breast cancer. Further xenograft experiment also showed that miR-320a could inhibit breast cancer metastasis in vivo. Our findings clearly demonstrate that miR-320a suppresses breast cancer metastasis by directly inhibiting MTDH expression. The present study provides a new insight into anti-oncogenic roles of miR-320a and suggests that miR-320a/MTDH pathway is a putative therapeutic target in breast cancer.
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