To understand the possible mechanism, the expression of related proteins in U2OS cells was detected by western blotting after RNA interference inhibited the expression of SIK2. The results showed that SIK2 gene silencing down-regulated the expression of MMP-2 and β-catenin, suggesting that these factors may work together to play an important role in the occurrence, development, invasion, and metastasis of osteosarcoma. Here, SIK2 is linked to osteosarcoma.