Glutathione peroxidase 4 mRNA (GPX4 mRNA) (GPX4 mRNA)

Glutathione peroxidase 4 (GPX4) mRNA is the messenger RNA transcript that encodes the GPX4 enzyme, a primary protector against ferroptosis, an iron-dependent form of regulated cell death [1]. The resulting GPX4 protein is the only enzyme capable of reducing complex lipid hydroperoxides within biological membranes to non-toxic lipid alcohols, thereby maintaining membrane integrity and preventing lethal lipid peroxidation [2]. In clinical research, GPX4 mRNA is targeted primarily in oncology, as many aggressive, mesenchymal, or drug-resistant tumors overexpress GPX4 to survive high levels of oxidative stress [3]. Therapeutic strategies targeting this mRNA include the use of small interfering RNAs (siRNAs) and antisense oligonucleotides (ASOs) to silence its expression and induce ferroptosis in malignant cells [4]. Beyond cancer, the regulation of GPX4 mRNA is studied in neurodegenerative diseases and cardiovascular conditions where oxidative damage plays a central role [5]. Because GPX4 is essential for the survival of many normal cell types, including neurons and renal cells, targeting its mRNA requires precise delivery systems to avoid systemic toxicity [6]. The mRNA levels of GPX4 serve as a critical biomarker for predicting the sensitivity of various cell lines to ferroptosis-inducing agents [7]. Experimental evidence suggests that knocking down GPX4 mRNA can sensitize tumors to conventional chemotherapies and immunotherapies by lowering the threshold for oxidative cell death [8].

Other names

PHGPx mRNAGPX4 transcriptPhospholipid hydroperoxide glutathione peroxidase mRNAGPX4 messenger RNA

RNA interference (RNAi) or RNase H-mediated degradation of the mRNA transcript to prevent the translation of the GPX4 protein, thereby inducing ferroptosis in target cells.