Nrf2-lncRNA controls cell fate by modulating p53-dependent Nrf2 activation as an miRNA sponge for Plk2 and p21.

Long noncoding RNA (lncRNA) capable of controlling antioxidative capacity remains to be investigated. Nuclear factor erythroid-2-related factor 2 (Nrf2) is a central molecule for cellular defense that increases antioxidative capacity. We identified a novel lncRNA named Nrf2-activating lncRNA () transcribed from an upstream region of the microRNA 122 gene (). existed in the cytoplasm, suggestive of its function as a competing endogenous RNA [ceRNA, microRNA (miRNA) sponge]. served as a ceRNA for polo-like kinase (Plk) 2 and cyclin-dependent kinase inhibitor 1 (p21) through binding of miRNA 128 and miRNA 224, inducing Plk2/Nrf2/p21 complexation for Nrf2 activation in the cells under p53-activating conditions (, DNA damage and serum deprivation). expression was suppressed with the initiation of apoptosis, being a rheostat for cell fate determination. levels correlated with the recurrence-free postsurgery survival rate of patients with hepatocellular carcinoma. Collectively, promotes Plk2 and p21 translation by competing for specific miRNAs and activating Nrf2 under surviving conditions from oxidative stress, implying that serves as a fine-tuning rheostat for cell fate decision.-Joo, M. S., Shin, S.-B., Kim, E. J., Koo, J. H., Yim, H., Kim, S. G. Nrf2-lncRNA controls cell fate by modulating p53-dependent Nrf2 activation as an miRNA sponge for Plk2 and p21.