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Oncotarget. 2016 Jun 21;7(25):38612-38625. doi: 10.18632/oncotarget.9572.

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

Author information

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.

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.

KEYWORDS:

MTDH; breast cancer; metastasis; miR-320a

PMID:
27229534
PMCID:
PMC5122415
DOI:
10.18632/oncotarget.9572
[Indexed for MEDLINE]
Free PMC Article

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