M6A-mediated silencing of RNF41 by METTL3/YTHDC1 disrupts autophagy to drive intervertebral disc degeneration.

ABSTRACT:

Background

Intervertebral disc (IVD) degeneration (IDD) represents a predominant origin of low back pain and disability, yet current therapeutic interventions remain suboptimal. Emerging evidence highlights autophagy activation as a therapeutic strategy against IDD. This study investigates the mechanistic interplay between N6-methyladenosine (m6A) modifications and autophagy dysregulation in IDD pathogenesis.

Methods

Bioinformatics analysis identified ring finger protein 41 (RNF41) as a key autophagy-IDD intersection gene. Functional validation utilized tert-butyl hydroperoxide (TBHP)-treated human nucleus pulposus (NP) cells to assess RNF41's effects on senescence (CDKN2A), autophagy (LC3-II/p62), apoptosis (TUNEL), inflammation (IL-18/IL-1β), and extracellular matrix (ECM)

SUBMITTER: Yao B 

PROVIDER: S-EPMC12580432 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature