To investigate whether the MAPK/ERK signaling act downstream of TRIM26, we examined the phosphorylation of ERK1/2 and its kinase (MEK1/2) in osteosarcoma cells after TRIM26 overexpression and knockdown, and our results showed that TRIM26 negatively regulates MEK/ERK signaling cascade in osteosarcoma cells. This evidence concerns the gene MAPK3 and osteosarcoma.