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

Autor: Yu J; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Wang JG; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.; Department of Pathology, The Affiliated Hospital of Qingdao University, Qingdao 266003, China., Zhang L; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Yang HP; Department of Pathology, People's Hospital, Linzi District, Zibo 255400, China., Wang L; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Ding D; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Chen Q; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Yang WL; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Ren KH; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Zhou DM; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China., Zou Q; Department of Breast Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China., Jin YT; Department of Breast Surgery, Huashan Hospital, Fudan University, Shanghai 200040, China., Liu XP; Department of Pathology, School of Basic Medical Sciences, Fudan University, Shanghai 200032, China.; Department of Pathology, The Fifth People's Hospital, Fudan University, Shanghai 200240, China.
Jazyk: angličtina
Zdroj: Oncotarget [Oncotarget] 2016 Jun 21; Vol. 7 (25), pp. 38612-38625.
DOI: 10.18632/oncotarget.9572
Abstrakt: 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.
Competing Interests: None.
Databáze: MEDLINE