Institute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, PR China.
Institute of Aging Research, Guangdong Provincial Key Laboratory of Medical Molecular Diagnostics, The First Dongguan Affiliated Hospital, Guangdong Medical University, Dongguan, PR China.
Biochem Biophys Res Commun. 2022 May 14;604:88-95. doi: 10.1016/j.bbrc.2022.03.041. Epub 2022 Mar 10.
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.
环状 RNA(circRNAs),作为单链闭合环状 RNA 分子,已被证实能在各种生物或病理过程中发挥关键作用。然而,circRNAs 对衰老和与衰老相关疾病的影响及其潜在机制仍不清楚。我们在此比较了年轻和衰老的小鼠胚胎成纤维细胞(MEFs)中 circRNAs 的表达模式,发现与年轻的 MEFs 相比,衰老的 MEFs 中 circRNF169 的表达水平显著上调。因此,我们进一步研究了 circRNF169 在 MEFs 衰老过程中的作用及其潜在机制。衰老相关-β-半乳糖苷酶染色和 BrdU 掺入试验的结果表明,circRNF169 的沉默显著延缓了 MEFs 的衰老并促进了细胞增殖,而 circRNF169 的异位表达则产生了相反的效果。此外,双荧光素酶报告基因实验证实,circRNF169 作为内源性 miR-30c-5p 的海绵体,通过隔离和抑制 miR-30c-5p 的活性来加速细胞衰老。综上所述,我们的研究结果表明,circRNF169 通过海绵吸附 miR-30c-5p 在细胞衰老中发挥着重要作用,并为衰老干预提供了一个有前景的靶点。