Apoptotic protease activating factor-1 negatively regulates Wnt signaling in hepatocellular carcinoma

Abstract

The current study aims to evaluate the mechanism of apoptotic protease activating factor-1 (Apaf-1) in hepatocellular carcinoma (HCC) cells by verifying the regulation of the wnt/beta-catenin signaling pathway via Apal-1. Our data showed that transfection with Ad-Apaf-1 could inhibit the activity of a lymphoid enhancer factor (LEF) luciferase plasmid activated by β-catenin. Overexpressing Apaf-1 could suppress the β-catenin-induced LEF luciferase activity in a dose-dependent manner. Western blot assays demonstrated that the overexpression of Apaf1 significantly suppressed the expression of Wnt/β-catenin signaling-related proteins. Further study demonstrated that Apaf-1 suppressed HepG2 cell migration, invasion, and viability. Knocking down the expression of Apaf-1 activated the wnt/β-catenin pathway in HepG2 cells. In contrast, silencing β-catenin decreased the activation of wnt/β-catenin, even in the presence of si-Apaf-1. Cell cycle distribution analysis demonstrated a decrease in the number of cells in the G0/G1 phase in the Apaf-1 silencing group. In contrast, knocking down the expression of β-catenin increased the number of cells in the G0/G1 phase, even in the presence of si-Apaf-1. In summary, the Apaf-1-mediated suppression of HepG2 cell malignancy is achieved by inhibiting the wnt/β-catenin pathway.