Targeting ferroptosis by noncoding RNAs as a novel therapeutic strategy for hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC), the most common primary liver cancer, is recognized as the third leading cause of cancer-related deaths. Late diagnosis and limited treatment efficacy are among the major challenges of HCC. Recent studies have introduced ‘ferroptosis’—a unique iron-dependent cell death mechanism driven by lipid peroxidation, accumulation of reactive oxygen species (ROS), and oxidative imbalance—as a promising therapeutic approach for HCC. It has also been shown that non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play key roles in the pathogenesis of HCC and the regulation of ferroptosis. Overall, ncRNAs regulate iron metabolism, antioxidant systems, and oxidative stress responses. These interactions influence HCC proliferation, invasion, and drug resistance. This review elucidates the role of ferroptosis in HCC, examines the regulation of ferroptosis pathways by ncRNAs, evaluates their therapeutic potential, and provides insights into novel strategies to improve HCC treatment outcomes.