MicroRNA-320a inhibits breast cancer metastasis by targeting metadherin.

// Juan Yu 1, * , Ji-Gang Wang 1, 2, * , Lei Zhang 1 , Hai-Ping Yang 3 , Lei Wang 1 , Di Ding 1 , Qi Chen 1 , Wen-Lin Yang 1 , Ke-Han Ren 1 , Dan-Mei Zhou 1 , Qiang Zou 4 , Yi-Ting Jin 4 , Xiu-Ping Liu 1, 5 1 Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China 2 Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China 3 Department of Pathology, People’s Hospital, Linzi District, Zibo 255400, China 4 Department of Breast Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China 5 Department of Pathology, The Fifth People’s Hospital, Fudan University, Shanghai 200240, China * These authors contributed equally to this work and are co-first authors Correspondence to: Xiu-Ping Liu, email: xpliu1228@fudan.edu.cn Yi-Ting Jin, email: clara_raky@aliyun.com Keywords: miR-320a, MTDH, metastasis, breast cancer Received: September 05, 2015     Accepted: May 01, 2016     Published: May 24, 2016 ABSTRACT 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.