MicroRNA-182 promotes proliferation and metastasis by targeting FOXF2 in triple-negative breast cancer

摘要

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer (BC), is characterized as high proliferation, young age and poor prognosis. MicroRNA-182 (miR-182) was reported to have oncogenic potential in many cancers. We aimed to elucidate pathobiological effects of miR-182 expression by targeting forkhead-box F2 (FOXF2) in TNBC. In this study, we explored the functional role of miR-182 expression in TNBC. Quantitative real-time PCR (qRT-PCR) was applied to evaluate the expression of miR-182 in cell lines and tissues. A series of in vitro and in vivo assays were performed in the MCF-7 and MDA-MB-231 cell lines with miR-182 overexpression. Luciferase reporter assays and western blot analysis were used to identify FOXF2 as the direct and functional target of miR-182. In TNBC tissues and cell lines, we found that miR-182 was significantly upregulated. Transwell assay showed that re-expression of miR-182 increased cell migration and invasion abilities and MTT assay showed that it promoted cell growth in vitro. In vivo assay, re-expression of miR-182 significantly increase tumor volume and enhanced instant metastasis in the lungs of mice. Besides, FOXF2 was identified as a direct and functional target of miR-182. These results indicated that miR-182 plays an important role in the initiation and progression of TNBC by targeting FOXF2 and the miR-182/FOXF2 axis may present a new therapeutic strategy for TNBC in the future.