Nuclear factor erythroid 2-related factor 2 (NRF2) mRNA (NFE2L2 mRNA)

Nuclear factor erythroid 2-related factor 2 (NRF2) mRNA, encoded by the NFE2L2 gene, is the transcript responsible for the synthesis of the NRF2 protein, a master regulator of the cellular antioxidant response [1, 2]. Under physiological conditions, NRF2 protein levels are kept low through Keap1-mediated degradation, but targeting the mRNA directly allows for the modulation of this pathway independently of the Keap1-NRF2 protein interaction [3]. In oncology, NRF2 mRNA is often overexpressed in various cancers, contributing to "NRF2 addiction" where tumor cells exploit antioxidant pathways to survive oxidative stress and resist therapy [3, 5]. Conversely, the delivery of synthetic NRF2 mRNA via lipid nanoparticles is being investigated as a therapeutic approach to enhance cytoprotection in conditions like acute lung injury, wound healing, and neurodegeneration [4]. Current RNA-based strategies include siRNA and antisense oligonucleotides (ASOs) for silencing NRF2 in cancer, as well as mRNA-based therapies for protein augmentation in inflammatory diseases [4, 5]. A primary therapeutic challenge is the "NRF2 paradox," where the pathway acts as a tumor suppressor during early carcinogenesis but promotes the survival of established malignant cells [5]. Small molecule drugs like Bardoxolone methyl and Omaveloxolone also interact with this pathway by stabilizing the protein product of the mRNA [3]. Overall, NRF2 mRNA represents a versatile target for both inhibition in cancer and induction in degenerative diseases.

Other names

NFE2L2 mRNANuclear factor erythroid-derived 2-like 2 mRNANRF2 transcript

Modulation of NRF2 protein expression through RNA interference (siRNA), antisense-mediated degradation (ASO), or translation of exogenous mRNA templates to restore or inhibit the antioxidant response pathway.