Long Non-Coding RNA KCNQ1OT1 Regulates Protein Kinase CK2 Via miR-760 in Senescence and Calorie Restriction

초록

Long non-coding RNAs (lncRNAs) play important biological roles. Here, the roles of the lncRNA KCNQ1OT1 in cellular senescence and calorie restriction were determined. KCNQ1OT1 knockdown mediated various senescence markers (increased senescence-associated beta-galactosidase staining, the p53-p21(Cip1/WAF1) pathway, H3K9 trimethylation, and expression of the senescence-associated secretory phenotype) and reactive oxygen species generation via CK2 alpha downregulation in human cancer HCT116 and MCF-7 cells. Additionally, KCNQ1OT1 was downregulated during replicative senescence, and its silencing induced senescence in human lung fibroblast IMR-90 cells. Additionally, an miR-760 mimic suppressed KCNQ1OT1-mediated CK2 alpha upregulation, indicating that KCNQ1OT1 upregulated CK2 alpha by sponging miR-760. Finally, the KCNQ1OT1-miR-760 axis was involved in both lipopolysaccharide-mediated CK2 alpha reduction and calorie restriction (CR)-mediated CK2 alpha induction in these cells. Therefore, for the first time, this study demonstrates that the KCNQ1OT1-miR-760-CK2 alpha pathway plays essential roles in senescence and CR, thereby suggesting that KCNQ1OT1 is a novel therapeutic target for an alternative treatment that mimics the effects of anti-aging and CR.

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