Bufalin at 80 nmol/L activated the ERS-mediated IRE1-JNK pathway in HCC Huh-7 and HepG-2 cells and induced apoptosis, but subsequent studies showed that IRE1 upregulated Beclin-1 and autophagy-associated protein Atg5 levels, promoted the transformation of LC3-I to LC3-II, inhibited p62 expression, and triggered cytoprotective autophagy to counteract apoptosis (Hu et al., 2014). This evidence concerns the gene ERN1 and hepatocellular carcinoma.