College of Pharmacy, Seoul National University, Seoul, South Korea.
Research Institute of Pharmaceutical Sciences, Seoul National University, Seoul, South Korea.
FASEB J. 2019 Jul;33(7):7953-7969. doi: 10.1096/fj.201802744R. Epub 2019 Mar 21.
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.
长链非编码 RNA（lncRNA）能够控制抗氧化能力，但仍需研究。核因子红细胞 2 相关因子 2（Nrf2）是一种细胞防御的核心分子，可增加抗氧化能力。我们鉴定了一种新的 lncRNA，命名为 Nrf2 激活 lncRNA（），它来源于 microRNA 122 基因（）的上游区域。存在于细胞质中，表明其作为竞争性内源性 RNA [ceRNA，microRNA（miRNA）海绵]的功能。通过结合 miRNA 128 和 miRNA 224，作为 polo 样激酶（Plk）2 和细胞周期蛋白依赖性激酶抑制剂 1（p21）的 ceRNA，诱导 Plk2/Nrf2/p21 复合物形成，在 p53 激活条件下（DNA 损伤和血清剥夺）激活 Nrf2。随着细胞凋亡的开始，表达受到抑制，成为细胞命运决定的变阻器。在具有肝细胞癌的患者中，表达水平与手术后无复发生存率相关。总之，在应激条件下，通过竞争特定的 miRNAs 促进 Plk2 和 p21 的翻译，并激活 Nrf2，表明 lncRNA 作为细胞命运决定的微调变阻器。-Joo，M. S.，Shin，S.-B.，Kim，E. J.，Koo，J. H.，Yim，H.，Kim，S. G. Nrf2-lncRNA 通过作为 Plk2 和 p21 的 miRNA 海绵来调节 p53 依赖性 Nrf2 激活来控制细胞命运。
