Abstract: Objective To explore the potential regulatory relationship between apolipoprotein E (APOE) and Golgi membrane protein 73 (GP73) for elucidating its significance in the proliferation of liver cancer cells. Methods Online databases were checked for correlation between APOE and GP73 expression in liver cancer. Mice were divided into control and Apoe knockout groups, control and Gp73 knockout groups. Cell lines were divided into Gp73 knockdown group, Apoe knockdown group (transfected with small interference RNA or infected with lentivirus) and corresponding control, GP73 over-expression group, APOE over-expression group (transfected with over-expression plasmids) and corresponding control, GP73 low expression group (transfected with small interference RNA or treated with rapamycin) and control group. Western blot was used to detect APOE and GP73 protein expression, and CCK8 assay was used to detect cell proliferation. Results GP73 was negatively correlated with APOE in liver cancer (P＜0.001).GP73 deficiency did not alter APOE expression, while APOE deficiency enhanced GP73 expression in mice(P＜0.001). Consistently, GP73 did not affect APOE expression but APOE negatively regulated GP73 expression in liver cancer cells (P＜0.01). Besides, Apoe knockdown promoted mouse liver cancer cell proliferation(P＜0.01), which was reversed by GP73 inhibition (P＜0.001). Conclusions APOE suppresses GP73 expression. Inhibition of GP73 may reverse APOE knockdown-accelerated cell proliferation. Therefore, APOE inhibits cell proliferation through suppression of GP73 which may contribute to liver cancer progression and be targeted for the treatment of hepatic cancer.

Key words: apolipoprotein E, Golgi membrane protein 73, negative regulation, cell proliferation