Silencing circATXN1 in Aging Nucleus Pulposus Cell Alleviates Intervertebral Disc Degeneration via Correcting Progerin Mislocalization.

ABSTRACT: Circular RNAs (circRNAs) play a critical regulatory role in degenerative diseases; however, their functions and therapeutic applications in intervertebral disc degeneration (IVDD) have not been explored. Here, we identified that a novel circATXN1 highly accumulates in aging nucleus pulposus cells (NPCs) accountable for IVDD. CircATXN1 accelerates cellular senescence, disrupts extracellular matrix organization, and inhibits mitochondrial respiration. Mechanistically, circATXN1, regulated by heterogeneous nuclear ribonucleoprotein A2B1-mediated splicing circularization, promotes progerin translocation from the cell nucleus to the cytoplasm and inhibits the expression of insulin-like growth factor 1 receptor (IGF-1R). To demonstrate the therapeutic potential of circATXN1, siRNA targeting the

SUBMITTER: Yu C 

PROVIDER: S-EPMC10964222 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature