TSG101 Promotes SIAH1 Auto-Ubiquitination to Drive Migration and Invasion in Hepatocellular Carcinoma Cells

Our previous studies have demonstrated that seven in absentia homologue 1 (SIAH1), an E3 ubiquitin ligase, is downregulated in hepatocellular carcinoma (HCC) and regulates substrate ubiquitination. However, the molecular mechanisms governing reduced SIAH1 expression in HCC remain unclear. Here, a yeast two-hybrid experiment and co-immunoprecipitation assay identified tumour susceptibility gene 101 (TSG101) as a potential interacting protein of SIAH1. We found that TSG101 negatively regulated the expression of SIAH1. Besides, TSG101 is upregulated in HCC and associated with a poor prognosis. TSG101 promotes the migration and invasion of HCC cells by regulating SIAH1 expression. Molecularly, TSG101 promoted the auto-ubiquitination and degradation of SIAH1 via the proteasome pathway, thereby reducing its protein stability. Finally, the protein levels of SIAH1 were found to be inversely correlated with TSG101 in human HCC tissues. In summary, TSG101 is up-regulated in human HCC tissues and promotes the migration and invasion of HCC cells by inducing SIAH1 auto-ubiquitination and degradation.