Abstract

Ferroptosis, a form of regulated cell death characterized by iron-dependent lipid peroxidation, has been increasingly implicated in cancer progression. However, the mechanism of carcinoma progression is still unclear, especially in hepatocellular carcinoma (HCC). In this study, we identified several ferroptosis-related genes by using bioinformatics analysis, including KIF20A. In PLC and SNU449 HCC cell lines, the knockdown of KIF20A could decrease the proliferation and increase the levels of MDA, ferrous ions, and ROS. In Hep3B and SNU 398 HCC cell lines, the overexpression of KIF20A enhanced the proliferative capacity and reduced the levels of MDA, ferrous ions, and ROS. To explore downstream molecular targets, this study performed RNA-sequencing following KIF20A knockdown, identifying HMOX1 as a key downstream target gene. Knockdown of KIF20A upregulates the expression of HMOX1 at both mRNA and protein levels. Conversely, overexpression of this gene yielded opposite results. Furthermore, our findings indicate that KIF20A inhibits ferroptosis in HCC cells via the HMOX1/SLC7A11/GPX4 pathway.