Fig. 5. UBE2S promotes the ubiquitination of PTEN, enhancing HCC cell chemoresistance by activating AKT pathway.

A, B GSEA plots show the enrichment of gene upregulated in cancer cells upon the knockdown of PTEN between the HCC tissues with UBE2S^high and UBE2S^low (A), or between the HCC tissues with FOXM1^high and FOXM1^low (B). C, D GSEA plots show the enrichment of gene downregulated in PTEN-knockdown cancer cells between the HCC tissues with UBE2S^high and UBE2S^low (C), or between the HCC tissues with FOXM1^high and FOXM1^low (D). E, F PTEN protein levels were investigated in UBE2S-knockdown (E) or UBE2S-overexpression (F) MHCC-97L cells. G UBE2S (Upper) and PTEN (Lower) complexes were co-immunoprecipitated with UBE2S and PTEN antibodies and immunoblotted with the indicated antibodies. H MHCC-97L cells overexpressed indicated proteins were treated with MG132 (10 μM) for 8 h, and the ubiquitination levels of PTEN protein were investigated. I–M MHCC-97L cells infected with indicated lentiviral plasmids and treated with MK2206 (5 μM) or DMSO (control) for 8 h. The indicated protein levels (I) and cytotoxic effects upon 5-FU (J, K) and oxaliplatin (L, M) were investigated. N, O The OS curves based on UBE2S transcript levels between HCC subgroup of AKT low (N) or high (O) expression. P, Q The DFS curves based on UBE2S transcript levels between HCC subgroup of AKT low (P) or high (Q) expression. R, S The OS curves based on FOXM1 transcript levels between HCC subgroup of AKT low (N) or high (O) expression. T, U The DFS curves based on FOXM1 transcript levels in HCC subgroup of AKT low (T) or high (U) expression.