Long non-coding RNA DANCR increases spinal cord neuron apoptosis and inflammation of spinal cord injury by mediating the microRNA-146a-5p/MAPK6 axis

Eur Spine J. 2024 May;33(5):2056-2067. doi: 10.1007/s00586-024-08216-7. Epub 2024 Mar 29.

Abstract

Objective: This research was to unravel the impact of the lncRNA differentiation antagonizing non-protein coding RNA (DANCR)/microRNA (miR)-146a-5p/mitogen-activated protein kinase 6 (MAPK6) axis on spinal cord injury (SCI).

Methods: SCI mouse models were established and injected with si-DANCR or miR-146a-5p agomir. The recovery of motor function was assessed by Basso Mouse Scale. SCI was pathologically evaluated, and serum inflammatory factors were measured in SCI mice. Mouse spinal cord neurons were injured by H2O2 and transfected, followed by assessment of proliferation and apoptosis. DANCR, miR-146a-5p, and MAPK6 in tissues and cells were detected, as well as their relationship.

Results: DANCR increased and miR-146a-5p decreased in SCI. Silencing DANCR or enhancing miR-146a-5p stimulated the proliferation of mouse spinal cord neurons and reduced apoptosis. DANCR was bound to miR-146a-5p to target MAPK6. DANCR affected the proliferation and apoptosis of spinal cord neurons by mediating the miR-146a-5p/MAPK6 axis. Downregulating DANCR or upregulating miR-146a-5p improved inflammation, the destruction of spinal cord tissue structure, and apoptosis in SCI mice.

Conclusion: DANCR affects spinal cord neuron apoptosis and inflammation of SCI by mediating the miR-146a-5p/MAPK6 axis.

Keywords: Apoptosis; Inflammation; LncRNA DANCR; MAPK6; Proliferation; Spinal cord injury; microRNA-146a-5p.

MeSH terms

  • Animals
  • Apoptosis*
  • Inflammation / genetics
  • Inflammation / metabolism
  • Male
  • Mice
  • Mice, Inbred C57BL
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Mitogen-Activated Protein Kinase 6 / genetics
  • Mitogen-Activated Protein Kinase 6 / metabolism
  • Neurons* / metabolism
  • RNA, Long Noncoding* / genetics
  • RNA, Long Noncoding* / metabolism
  • Spinal Cord / metabolism
  • Spinal Cord / pathology
  • Spinal Cord Injuries* / genetics
  • Spinal Cord Injuries* / metabolism
  • Spinal Cord Injuries* / pathology

Substances

  • MicroRNAs
  • Mirn146 microRNA, mouse
  • Mitogen-Activated Protein Kinase 6
  • RNA, Long Noncoding