MicroRNA-1297 downregulation inhibits breast cancer cell epithelial-mesenchymal transition and proliferation in a FA2H-dependent manner

Breast cancer (BC) is one of the most common malignant tumors among women worldwide. MicroRNAs (miRs) may be involved in several types of human cancer, including gastric, liver, lung and breast cancer. The aim of the present study was to investigate the effect of miR-1297 on MDA-MB-231 cell epithelial-mesenchymal transition (EMT) and proliferation, and the underlying molecular mechanisms. MDA-MB-231 cells were transfected with miR-1297 inhibitor or inhibitor control for 48 h. Subsequently, MTT and flow cytometry assays indicated that miR-1297 inhibitor significantly decreased cell proliferation and induced apoptosis compared with the inhibitor control group. In addition, reverse transcription-quantitative PCR and western blotting suggested that miR-1297 inhibitor suppressed EMT in MDA-MB-231 cells compared with the inhibitor control group. TargetScan bioinformatics analysis and a dual-luciferase reporter gene assay were performed, which predicted that miR-1297 directly targeted fatty acid 2-hydroxylase (FA2H). Furthermore, MDA-MB-231 cells were transfected with control-plasmid or FA2H-plasmid for 48 h. The results demonstrated that FA2H overexpression decreased MDA-MB-231 cell proliferation and increased apoptosis compared with the control-plasmid group. Additionally, FA2H-plasmid increased E-cadherin expression levels, and reduced N-cadherin and matrix metalloproteinase 9 expression levels at both the protein and mRNA level compared with control-plasmid. Finally, MDA-MB-231 cells were transfected with control-small interfering (si)RNA, FA2H-siRNA, inhibitor control, miR-1297 inhibitor, miR-1297 inhibitor + control siRNA or miR-1297 inhibitor + FA2H-siRNA, and the results suggested that the biological effects of miR-1297 inhibitor were reversed by co-transfection with FA2H siRNA. In conclusion, the present study indicated that miR-1297/FA2H might serve as a novel potential biomarker and therapeutic target for BC.