Ferroptosis rewired: ncRNA gatekeepers as pharmacological targets in hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) can alter cellular programs, such as iron homeostasis and antioxidant defenses, creating a pathway to ferroptosis, an iron-dependent mechanism of cellular death, as a viable therapeutic approach. Non-coding RNAs (ncRNAs), including both microRNAs (miRNAs) and long non-coding RNAs (lncRNAs), have recently been shown to be potent regulatory molecules involved in gene expression and cell fates, including apoptosis and inflammation. This review summarizes the current literature regarding ncRNAs' multiple and complex roles in mediating HCC ferroptosis. We focus on mechanistic insights into how ncRNAs regulate some major ferroptosis regulators (e.g., SLC7A11/GPX4 axis, iron metabolism, and lipid peroxidation). We also highlight recent research evidence of the interconnection between ncRNA-modulated regulation of ferroptosis and inflammation in HCC development. This review thoughtfully evaluates studies that have identified ncRNAs functioning as either promoters or suppressors of ferroptosis and their impacts on the inflammatory response within the tumor microenvironment. Finally, we discuss the prognostic roles of these ncRNAs and the potential for ncRNAs to be used as diagnostic and therapeutic biomarkers in HCC. Finally, through an accumulated body of literature, we try to create a cohesive understanding of ncRNAs' role in ferroptosis and inflammation in HCC, pointing to promising avenues for future research and clinical applications.