The Mechanism Of USP18 Promoting The Apoptosis Of Liver Cancer Cells Induced By NDV

Hepatocellular carcinoma seriously endangers the health of humanity.There is no effective treatment currently.Newcastle Disease Virus(NDV)is an avian virus that can specifically infect and kill tumour cells.It has been demonstrated that oncolytic virus represented by NDV has potential application prospects in tumour therapy.The mechanisms of oncolytic effect of NDV are not clear.Further understanding of the mechanism of NDV oncolysis provides a theoretical basis for the rapid use of NDV for tumour treatment.USP18(Ubiquitin Specific Protease 18)is a deubiquitinated protease that specifically removes ubiquitin molecules from the substrates.We will explore the function and mechanism of USP18 in the apoptosis of liver cancer cells induced by NDV in the study.We found that the level of USP18 mRNA and protein was significantly up-regulated under NDV infection in liver cancer cells.Overexpression of USP18 significantly promoted the NDV-induced apoptosis of liver cancer cells.Conversely,silencing USP18 blocked the induction of apoptosis by NDV.Further studies shown that the overexpression of USP18 increased protein level of BAX and NOXA,promoted the release of cytochrome C,and enhanced the cleavage of caspase-7.Knocking down of USP18 decreased BAX and NOXA,inhibited the release of cytochrome C,and attenuated the cleavage of caspase-7.All the data suggested that the function of USP18 of promoting NDV-induced apoptosis of liver cancer cells is depended on mitochondrial apoptosis pathway.Our previous studies have shown that ISG12 a can induce apoptosis of liver cancer cells in mitochondrial apoptosis pathway-dependent manner.Moreover,we found that USP18 could stabilize ISG12 a protein,and can inhibit the ubiquitination of ISG12 a.All the data indicated that USP18 promotes NDV-induced apoptosis of liver cancer cells through stabilizing ISG12 a protein.Our findings provide a new target and a new horizon for the study and clinical treatment of hepatocellular carcinoma.