MARCH5 promotes hepatocellular carcinoma progression by inducing p53 ubiquitination degradation

Abstract Dysregulated MARCH5 expression and impaired autophagy have been reported separately in some cancers. However, their relationship has not been explored in hepatocellular carcinoma (HCC). Here, we report the up-regulated expression of MARCH5 in hepatocellular carcinoma (HCC) tissues. Biologically, We further demonstrated that MARCH5 stimulation promotes proliferation, migration and invansion of HCC cells in vitro and enhances tumourigenesis and metastasis in vivo. This phenotype could be reversed by knockdown of MARCH5. Mechanistically, MARCH5 activated hepatocellular carcinoma autophagy by inducing LC3I/LC3II conversion, which is essential for the biological function of MARCH5. We further demonstrated the interaction between MARCH5 and p53, which ubiquitinates degraded p53. in conclusion, MARCH5 promotes HCC proliferation, invasion, and migration by ubiquitinating p53 ubiquitination, adding an important layer to the linkage between MARCH5 and p53, which can be translated into a new targeted therapy.