Identification and Characterisation of Potential Targets for N6-methyladenosine (m6A) Modification during Intervertebral Disc Degeneration

Front Biosci (Landmark Ed). 2024 Nov 28;29(12):405. doi: 10.31083/j.fbl2912405.

Abstract

Background: The mechanism for RNA methylation during disc degeneration is unclear. The aim of this study was to identify N6-methyladenosine (m6A) markers and therapeutic targets for the prevention and treatment of intervertebral disc degeneration (IDD).

Methods: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and quantitative reverse transcription PCR (RT-qPCR) were employed to analyze m6A modifications of IDD-related gene expression. Bioinformatics was used to identify enriched gene pathways in IDD. m6A-RIP-qPCR was used to validate potential targets and markers.

Results and conclusion: Human IDD samples exhibited a distinct m6A modification pattern that allowed associated genes and pathways to be identified. These genes had functions such as "nuclear factor kappa-B (NF-κB) binding" and "extracellular matrix components", which are crucial for IDD pathogenesis. ANXA2 showed increased m6A modification in IDD, while SLC3A2 and PBX3 showed decreased m6A methylation. The results of this study offer novel insights for the prevention and treatment of IDD.

Keywords: N6-methyladenosine; RNA methylation; epigenetics; intervertebral disc degeneration; nucleus pulposus.

MeSH terms

  • Adenosine* / analogs & derivatives
  • Adenosine* / genetics
  • Adenosine* / metabolism
  • Adult
  • Computational Biology / methods
  • Female
  • Humans
  • Intervertebral Disc Degeneration* / genetics
  • Intervertebral Disc Degeneration* / metabolism
  • Male
  • Methylation
  • Middle Aged

Substances

  • Adenosine
  • N-methyladenosine