CircGLCE alleviates intervertebral disc degeneration by regulating apoptosis and matrix degradation through the targeting of miR-587/STAP1

Aging (Albany NY). 2020 Nov 6;12(21):21971-21991. doi: 10.18632/aging.104035. Epub 2020 Nov 6.

Abstract

The purpose of this study was to identify a specific circular RNA and to investigate its regulatory mechanism in intervertebral disc degeneration (IDD). CircGLCE was selected after microarray analyses and was further analysed by RT-qPCR and FISH. CircGLCE was found to stably exist in the cytoplasm of nucleus pulposus (NP) cells. It was downregulated in IDD. After silencing CircGLCE, its function was assessed with RT-qPCR, immunofluorescence analysis and flow cytometry. Knockdown of CircGLCE promoted apoptosis and induced the expression of matrix-degrading enzymes in NP cells. CircGLCE served as a miR-587 sponge in NP cells. Inhibiting miR-587 counteracted the IDD-enhancing effect caused by silencing CircGLCE. STAP1 served as the miRNA target that mediated the functions of miR-587. In an IDD mouse model, the in vivo effects of overexpressing CircGLCE on IDD were confirmed by imaging techniques, TUNEL staining, FISH, western blotting, H&E staining and immunohistochemistry. Thus, CircGLCE attenuates IDD by inhibiting the apoptosis of NP cells and ECM degradation through the targeting of miR-587/STAP1. CircGLCE may be a potential therapeutic target for IDD treatments.

Keywords: CircGLCE; apoptosis; intervertebral disc degeneration; miR-587; nucleus pulposus cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics
  • Adaptor Proteins, Signal Transducing / metabolism*
  • Animals
  • Apoptosis*
  • Cells, Cultured
  • Disease Models, Animal
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology*
  • Female
  • Gene Expression Regulation
  • Humans
  • Intervertebral Disc Degeneration / genetics
  • Intervertebral Disc Degeneration / metabolism*
  • Intervertebral Disc Degeneration / pathology
  • Male
  • Mice, Inbred C57BL
  • MicroRNAs / genetics
  • MicroRNAs / metabolism*
  • Middle Aged
  • Nucleus Pulposus / metabolism*
  • Nucleus Pulposus / pathology
  • RNA, Circular / genetics
  • RNA, Circular / metabolism*
  • Retrospective Studies
  • Signal Transduction

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN587 microRNA, human
  • MicroRNAs
  • RNA, Circular
  • STAP1 protein, human