The Role And Mechanism Of USP11 In The Resistance To Chemotherapy In Hepatocellular Carcinoma

Objective: This study aims to investigate the role of USP11 during chemotherapy resistance and its mechanism in hepatocellular carcinoma(HCC),thus providing support of developing new targets in HCC.Methods: Samples of human HCC tissues and the adjacent tissues from general surgery department of Tongji Hospital were collected and detected by Western blot and immunohistochemistry(IHC).Lentiviral transduction system was used to generate USP11 knock-down cells,which were then estimated for the sensitivity to cisplatin by CCK8 assay.Co-Immunoprecipitation was performed to verify the interaction between USP11 and PARP1.Western blot and q RT-PCR were used to detect the regulation between USP11 and PARP1.Protein half-life assay and degradation inhibition assay were performed to demonstrate the impact of USP11 to the PARP1 abundance.Ubiquitination assay was performed to examine the effect of USP11 on the ubiquitination level of PARP1.Results: We found that that USP11 expression was low in the normal liver tissues and increased in the HCC tissues.Knocking down of USP11 increased the sensitivity to cisplatin in HCC cells.USP11 could bind to PARP1 and remove poly-ubiquitin chains on PARP1,which prevented PARP1 degradation by ubiquitin-proteasome pathway,thus stablizing the expression of PARP1 in HCC cells.Conclusions: USP11 expression is upregulated during HCC genesis and progression.USP11 interacts with and deubiquitinates PARP1 to stablize its expression,which promotes chemotherapy resistance of HCC.