| Expression pattern: |
UP |
| Associated gene: |
PABPC4, FAM134B mRNA |
| Associated microRNA: |
- |
| Biological function: |
circFAM134B promotes lenvatinib-induced ferroptosis in HCC cells and regulates FAM134B-mediated ER-phagy; knockdown of circFAM134B weakens lenvatinib-induced growth inhibition, reduces Fe2+, MDA and ROS, increases GSH, and inhibits ferroptosis in vitro and in vivo. |
| Molecular mechanism: |
circFAM134B acts as a sponge that competitively binds the RNA-binding protein PABPC4, influencing FAM134B mRNA nonsense-mediated decay and thereby regulating FAM134B-mediated ER-phagy and lenvatinib-induced ferroptosis. |
| Biological pathway or process: |
ferroptosis (promotes); autophagy (inhibits); mRNA stability (inhibits); drug resistance (inhibits) |
| Detected method: |
Q
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; Flow Cytometry（Non-apoptosis/cycle）; Western Blot; IF (Immunofluorescence); In Vivo Animal Model; Bioinformatics Analysis |
| Clinical significance: |
Targeting circFAM134B-PABPC4-FAM134B axis may provide new ideas and strategies to address resistance to liver cancer treatment. |
| Description: |
This study identifies hsa_circ_0128505, abbreviated circFAM134B, as a regulator of lenvatinib-induced ferroptosis in HCC. Mechanistically, circFAM134B competitively binds PABPC4 and affects FAM134B mRNA nonsense-mediated decay, thereby modulating FAM134B-mediated ER-phagy and ferroptotic response. Targeting the circFAM134B-PABPC4-FAM134B axis is proposed as a potential strategy to improve treatment response in liver cancer. |
| Confidence score: |
0.7897 |