RNA Adenosine Deaminases Modulate Oxidative Stress-Mediated Hepatocellular Carcinoma Cell Damage via KEAP1/Nrf2 Axis

Abstract

This study investigates the role of RNA adenosine deaminases (ADAR1/2) in oxidative stress-induced Hepatocellular Carcinoma (HCC) cell damage. We demonstrate that hydrogen peroxide (H₂O₂)-mediated oxidative stress downregulates ADAR1/2 expression, impairing A-to-I RNA editing of antioxidant genes. Mechanistically, ADAR2 deficiency reduces KEAP1 editing, activating Nrf2 signaling and promoting HCC cell survival. These findings establish ADARs as critical regulators of redox homeostasis in HCC, providing novel therapeutic targets.