| Expression pattern: |
UP |
| Associated gene: |
ALKBH5, BCL-2, BECN1 |
| Associated microRNA: |
- |
| Biological function: |
Promotes sorafenib/Erastin-induced ferroptosis and increases cellular sensitivity to sorafenib; positively regulates autophagy flux and ferritinophagy in HCC cells. |
| Molecular mechanism: |
cIARS physically binds the RNA-binding protein ALKBH5 and represses ALKBH5-mediated autophagy inhibition; through this cIARS-ALKBH5 interaction, cIARS promotes autophagy/ferritinophagy and thereby enhances ferroptosis during sorafenib treatment. |
| Biological pathway or process: |
ferroptosis (promotes); autophagy (promotes); ferritinophagy (promotes) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; RNA EMSA; CCK8; Western Blot |
| Clinical significance: |
- |
| Description: |
In sorafenib-treated HCC cell lines, cIARS (hsa_circ_0008367, from IARS) is upregulated and promotes ferroptosis and drug cytotoxicity. Mechanistically, it binds the RBP ALKBH5 and counteracts ALKBH5-driven autophagy inhibition, thereby enhancing autophagic flux/ferritinophagy to support ferroptotic events. |
| Confidence score: |
0.7742 |