OTUB1 Promotes HCC Progression by Regulating Glycolysis Through Deubiquitination of PKM2

Hepatocellular carcinoma (HCC) is a highly prevalent malignant tumor worldwide, and dysregulation of ubiquitination is an important factor promoting HCC progression. OTUB1 (OTU domain-containing ubiquitin aldehyde-binding protein 1) has been shown to be associated with the progression of various Tumors. However, its role in HCC remains unclear. In this study, based on bioinformatics analysis, we found that OTUB1 expression is upregulated in HCC tissues. In vitro and in vivo functional assays demonstrated that OTUB1 overexpression enhances the proliferation and invasion abilities of HCC cells and promotes tumor progression in mice. Mechanistically, OTUB1 promotes aerobic Glycolysis in HCC by mediating the deubiquitination and stabilization of Pyruvate Kinase isoform M2 (PKM2), and this effect can be reversed by PKM2 knockdown. In conclusion, our findings indicate that OTUB1 enhances aerobic Glycolysis by regulating the stability of PKM2 protein, thereby driving HCC progression.