GSE115409
NACER, a liver-specific lncRNA, functions as Nrf2-activating competing endogenous RNA for Plk2 and p21cip1
LncRNA for anti-oxidative capacity control has not been discovered yet. Nrf2 is a central molecule for cellular defense by increasing anti-oxidative capacity. Here, we identified a novel lncRNA named 'NACER' (Nrf2 Activating Competing Endogenous RNA) transcribed from an upstream region of MIR122. NACER existed in the cytoplasm, suggestive of its function as competing endogenous RNA (ceRNA, miRNA sponge). NACER served as ceRNA for Plk2 and p21cip1 through binding for miR-128/224, inducing Plk2/Nrf2/p21cip1 complexation for Nrf2 activation in cells under p53-activating conditions (i.e., DNA damage and serum deprivation). NACER expression was suppressed when apoptosis was initiated, being a rheostat for cell fate determination. NACER levels correlated with the recurrence free survival rate of patients with hepatocellular carcinoma after surgery. Collectively, NACER promotes Plk2 and p21cip1 translation by competing for specific miRNAs, activating Nrf2 under the surviving condition from oxidative stress, implying that NACER plays a fine-tuning rheostat for cell fate decision. Overall design: Examination of RNA expression in Huh7 cells after NACER knockdown