The anti-tumor effects of Mfn2 in breast cancer are dependent on promoter DNA methylation, the P21 motif and PKA phosphorylation site.

() is expressed in numerous human tissues and serves a pivotal role in cell proliferation. However, Mfn2 is considered as an anti-tumor gene, and is silenced in human malignant tumors, including those of breast cancer. However, the mechanisms contributing to silencing and the mechanism of its anti-tumor function in breast cancer remain unclear. In the present study, hypoexpression of , and hypermethylation of its promoter, was confirmed in human breast cancer cells and in breast cancer tissues by reverse transcription-quantitative polymerase chain reaction (PCR) and methylation specific PCR, respectively. Chemical demethylation treatment with 5-aza-2'-deoxycytidine upregulated the mRNA expression level of in MCF-7 cells in a dose-dependent manner. In addition, overexpression of repressed the proliferation, migration and invasion of MCF-7 cells, mediated by inhibition of the Ras-extracellular signal-regulated kinase (ERK)1/2 signaling pathway. However, overexpression of with deletion of the p21 motif () and protein kinase A (PKA) phosphorylation site () partially reduced the anti-tumor function of Mfn2, and inhibited the Ras-ERK1/2 signaling pathway. Taken together, the present study confirmed the anti-tumor effects of Mfn2 in human breast cancer and clarified that the mechanism of its anti-tumor functions includes promoter DNA methylation, the P21 binding site and PKA phosphorylation.