Oxidative Stress-Induced ADAR1/2 Dysfunction Promotes Hepatocellular Carcinoma Cell Damage via Redox Imbalance

Abstract

Hepatocellular Carcinoma (HCC) progression is tightly linked to oxidative stress, yet the role of RNA Adenosine Deaminases (ADARs) in this process remains unclear. Here, we demonstrate that hydrogen peroxide (H₂O₂)-induced oxidative stress downregulates ADAR1/2 expression in HCC cells, leading to reduced A-to-I RNA editing and exacerbated cell damage. Mechanistically, ADAR loss impaired antioxidant defense by dysregulating SOD2/CAT expression and disrupting Nrf2 signaling. Our findings establish ADARs as critical regulators of redox homeostasis in HCC, offering novel therapeutic opportunities.