Circular RNA circRNF169 functions as a miR-30c-5p sponge to promote cellular senescence

环状 RNA circRNF169 作为 miR-30c-5p 海绵发挥作用,促进细胞衰老

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作者:Dingyuan Zhang, Yuting Li, Yiting Lei, Haiqing Yang, Linying Huang, Xue Chen, Zhihao Zhou, Cuiyi Huang, Yantao Zhou, Ruolan Feng, Xing-Dong Xiong, Yuan Yuan, Hongjing Cui, Hui-Ling Zheng, Xuerong Sun, Xinguang Liu, Shun Xu

Abstract

Circular RNAs (circRNAs), characterized as single-stranded closed circular RNA molecules, have been established to exert pivotal functions in various biological or pathological processes. Nonetheless, the effects and underlying mechanisms concerning circRNAs on the aging and aging-related diseases remain elusive. We herein compared the expression patterns of circRNAs in young and senescent mouse embryonic fibroblasts (MEFs), and uncovered that circRNF169 was dramatically up-regulated in senescent MEFs compared with that in young MEFs. Therefore, we further digged into the role and potential mechanisms of circRNF169 in the senescence of MEFs. The results of senescence-associate-β-galactosidase staining and BrdU incorporation assay showed that silencing of circRNF169 significantly delayed MEFs senescence and promoted cell proliferation, while ectopic expression of circRNF169 exhibited the opposite effects. Moreover, the dual-luciferase reporter assay confirmed that circRNF169 acted as an endogenous miR-30c-5p sponge, which accelerated cellular senescence by sequestering and inhibiting miR-30c-5p activity. Taken together, our results suggested that circRNF169 exerted a crucial role in cellular senescence through sponging miR-30c-5p and represented a promising target for aging intervention.

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