Molecular Mechanism Of Deubiquitinase USP14 In Promoting Growth And Metastasis Of Hepatocellular Carcinoma

Hepatocellular carcinoma(HCC)is one of the most lethal cancers.It has been reported that protein deubiquitination plays an important role in tumour progression.USP14 can promote the occurrence and development of several tumors as a deubiquitinase enzyme.However,the function and potential molecular mechanism of USP14 in HCC have not been fully clarified.We detected the expression level of USP14 in 110 pairs of HCC and adjacent nontumor tissues by immunohistochemisty,and the results showed that USP14 was highly expressed in HCC tissues.The high expression of USP14 was significantly related to tumor size,tumor metastasis,relapse free survival(RFS)and overall survival(OS).Functional experimets demonstrated that USP14 could promote the growth and metastasis of HCC cells.Further mechanism study revealed that USP14 could interact with MEP50.USP14 did not affect the expression of MEP50.USP14 regulated of the downstream genes of MEP50 via reducing the K63-linked ubiquitination level of MEP 50.Finally,we found that IU1,a specific USP14 inhibitor,significantly inhibited the proliferation,migration and invasion of HCC cells.Conclusion:USP14 is highly expressed in HCC,which can promote the growth,invasion and metastasis of HCC.USP14 can affect the expression of downstream genes by regulating the ubiquitination level of MEP50,then regulate the occurrence and development of HCC.This study provides an important theoretical basis for USP14 as a specific therapeutic target for HCC therapy.