USP22 and hepatocellular carcinoma: Furthermore, the simultaneous release of sorafenib and USP22 shRNA (shUSP22) by galactose-modified lipopolysaccharide revealed that the encapsulated sorafenib along with shUSP22 could obtain a synergistic anti-proliferative effect in HCC cells by inducing reactive oxygen cascade to promote the release of shUSP22 and inhibit the expression of USP22 in HCC cells, which promoted the accumulation of sorafenib by downregulating the expression level of multidrug resistance-related proteins[99].