miR-616 promotes breast cancer migration and invasion by targeting TIMP2 and regulating MMP signaling

Abstract

Breast cancer is one of the most frequently diagnosed cancer types in females worldwide. The aim of the present study was to investigate the expression levels, functional role and molecular mechanism of microRNA-616 (miR-616) in the progression of breast cancer cells. The relative expression levels of miR-616 in breast cancer cell lines and tumor tissues of 30 patients with breast cancer were analyzed using reverse transcription-quantitative PCR (RT-qPCR). Cell transfection was used to upregulate and downregulate the expression of miR-616 in MCF-7 and MDA-MB-231 cells, respectively. The regulatory effect of miR-616 on tissue inhibitor of metalloproteinases 2 (TIMP2) expression was also analyzed by dual-luciferase reporter assay, western blot analysis and RT-qPCR. The results of RT-qPCR analysis demonstrated significantly higher expression levels of miR-616 in tumor tissues and cancer cell lines compared with normal tissues and a normal epithelial cell line. In addition, overexpression of miR-616 significantly promoted MCF-7 cell proliferation, migration and invasion. By contrast, miR-616 silencing was associated with the opposite effects in MDA-MB-231 cells. Furthermore, the present study demonstrated that miR-616 could positively regulate the expression of matrix metalloproteinases (MMP)2 and MMP9, both at the mRNA and protein level. TIMP2 was further confirmed as a direct target of miR-616. Finally, the current study demonstrated that TIMP2 silencing rescued the proliferation and invasion capabilities and the expression levels of MMP2 and MMP9 in cells that were treated with the miR-616 inhibitor. In conclusion, the present data suggested that the miR-616/TIMP2/MMPs axis may serve an important role in the progression of breast cancer and may be a potential therapeutic target for this disease.