NS3 can also interact with several components of the UPS, including the E3 ubiquitin ligase components DDB1 [33], LUBAC [34], and SMURF2 [12], which suggests that the utilization of the UPS by HCV proteins has become one of the strategies of HCV for promoting HCC progression and viral replication. This evidence concerns the gene KRAS and hepatocellular carcinoma.