MiR-214 promotes carcinogenesis in triple-negative breast cancer by inhibiting FRK expression

Background: Triple-negative breast cancer (TNBC) is known to have a poor prognosis with limited treatment options. In-house data revealed that miR-214 was up-regulated in breast cancer tissue, but there have been conflicting results about the role of miR-214 in oncogenesis in breast cancer. In this study, we aimed to investigate the potential role of miR-214 and its target in carcinogenesis. Methods: We used three breast cancer cell lines (MCF-7, MDA-MB-231, and MDA-MB-468) and control breast epithelial cell line (MCF-10A) to evaluate miR-214 expression and function. Target genes were predicted based on pre-formed miRNA databases. miR-214 was transfected into cell lines, and cell proliferation, invasion and migration assays, and RT-PCR analysis were performed. Results: MiR-214 was significantly overexpressed in MDA-MB-231 line, which represents TNBC. Fyn-related kinase (FRK) was selected as a potential target of miR-214. Endogenous FRK levels were down-regulated in MDA-MB-231 cells. miR-214 transfected MDA-MB-231 cell line resulted in increased cell proliferation, and silencing FRK using si-FRK also induced cell proliferation in MDA-MB-231 cells. When MDA-MB-231 cells were transfected with miR-214, cell invasion and migration were enhanced. Furthermore, si-FRK-transfected MDA-MB-231 cells showed increased cell invasion and migration compared to the control cells. Conclusions: Our results suggest that miR-214 might play a role in tumor proliferation and invasion to promote breast cancer oncogenesis by suppressing FRK activity, leading to cancer progression.