| Expression pattern: |
UP |
| Associated gene: |
heterogeneous nuclear ribonucleoprotein A2B1, HNRNPA2B1, progerin, insulin-like growth factor 1 receptor, IGF-1R, IGF-1Rbeta, pre-ATXN1 |
| Associated microRNA: |
- |
| Biological function: |
Promotes cellular senescence/aging of nucleus pulposus cells, disrupts extracellular matrix organization, and inhibits mitochondrial respiration; circATXN1 silencing rejuvenates aging hNPCs and delays IVDD in vivo. |
| Molecular mechanism: |
HNRNPA2B1-mediated splicing circularization regulates circATXN1 formation (linked to m6A in pre-ATXN1 intron 5); circATXN1 binds progerin and promotes its translocation from nucleus to cytoplasm, leading to reduced IGF-1Rbeta expression/signaling and promoting senescence/IVDD. |
| Biological pathway or process: |
proliferation (inhibits); mitochondrial function (inhibits); ceRNA regulation (inhibits); ECM (other) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; RNase R Treatment; Sanger Sequencing; Back-Splice Junction PCR / divergent primers PCR; Agarose gel electrophoresis; FISH / smFISH; RIP (RNA Immunoprecipitation); RNA Pull-Down; Western Blot; Transfection; CCK8; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; H&E Staining |
| Clinical significance: |
CircATXN1 was enriched in the nucleus pulposus tissues of IVDD patients. |
| Description: |
circATXN1 (hsa_circ_0007909) is up-regulated in aging human nucleus pulposus cells/tissues in IVDD and promotes senescence, ECM disruption, and impaired mitochondrial respiration. It is regulated by HNRNPA2B1-associated circularization and binds progerin to drive its nucleus-to-cytoplasm translocation, suppressing IGF-1Rbeta signaling. Silencing circATXN1 via an siRNA-loaded DNA tetrahedron nanogel reverses aging phenotypes in hNPCs and alleviates IVDD in zmpste24-/- mice. |
| Confidence score: |
0.7846 |