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

Biochem Biophys Res Commun. 2022 May 14:604:88-95. doi: 10.1016/j.bbrc.2022.03.041. Epub 2022 Mar 10.

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.

Keywords: Aging; Cellular senescence; CircRNF169; miR-30c-5p.

MeSH terms

  • Animals
  • Cell Proliferation / genetics
  • Cellular Senescence* / genetics
  • Fibroblasts / metabolism
  • Mice
  • MicroRNAs* / genetics
  • MicroRNAs* / physiology
  • RNA, Circular* / genetics
  • RNA, Circular* / physiology

Substances

  • MicroRNAs
  • RNA, Circular