<scp>USP22</scp> Promotes Osteosarcoma Progression by Stabilising β‐Catenin and Upregulating <scp>HK2</scp> and Glycolysis

Osteosarcoma is a primary malignancy that is difficult to treat and is prone to developing resistance to chemotherapy. As such, it is necessary to continuously explore novel therapeutic targets. Ubiquitin-specific protease 22 (USP22) is an ubiquitin-specific protease that has been demonstrated to have potent carcinogenic effects on a variety of cancers and is involved in several biological processes. Studies have demonstrated that reprogramming of glucose metabolism is a major factor in the development and progression of osteosarcoma, and that USP22 is strongly associated with the metabolism of glucose in osteosarcoma. However, it is still unknown how precisely USP22 works in osteosarcoma. To further elucidate the expression and specific molecular mechanisms of USP22 in osteosarcoma. The results of Western blot analysis and quantitative reverse transcription polymerase chain reaction (qRT-PCR) showed that the expression of USP22 in osteosarcoma tissues was significantly higher than that in adjacent healthy tissues. In addition, the expression of USP22 promotes the proliferation of osteosarcoma cells in a glycolytic dependent manner both in vitro and in vivo, while the knockout of USP22 is the opposite. In addition, USP22 knockout reduced the protein expression of β-catenin and hexokinase 2 (HK2) in osteosarcoma cells. In addition, the regulation of HK2 expression induced by USP22 depends on β-catenin. Mechanistically, USP22 regulates HK2 by deubiquitination and stabilising the expression of β-catenin, thereby controlling glycolysis in osteosarcoma cells.