| Expression pattern: |
DN |
| Associated gene: |
beta-catenin, YTHDF3, LIN28, CCND1, CMYC |
| Associated microRNA: |
hsa-Let-7d-5p / Let-7d |
| Biological function: |
inhibits cancer stem cell renewal; resensitizes Osimertinib-resistant LUAD cells to Osimertinib; suppresses Wnt/beta-catenin signaling |
| Molecular mechanism: |
m6A-dependent translation of circFBXW7 into circFBXW7-185AA, which binds beta-catenin and promotes its ubiquitination to inhibit canonical Wnt/beta-catenin signaling; forms feedback with Let-7d and YTHDF3 |
| Biological pathway or process: |
Wnt/beta-catenin (inhibits); stemness (inhibits); proliferation (inhibits); ceRNA regulation (other); ubiquitination (promotes) |
| Detected method: |
Q
S
M
|
| Validation methods: |
RNA-seq; Microarray; RT-qPCR; Bioinformatics Analysis; Luciferase Reporter Assay; Transfection; Co-IP; Western Blot; CCK8; EdU Staining; Colony Formation Assay; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; Survival Analysis; ROC Analysis; MeRIP / MeRIP-seq |
| Clinical significance: |
reverses resistance to TKIs (Osimertinib) and determines cellular response to Osimertinib |
| Description: |
circFBXW7 is down-regulated in Osimertinib-resistant LUAD cells/stem-like cells and its abnormal level affects drug response. It can be translated (m6A/YTHDF3-dependent) into circFBXW7-185AA, which binds beta-catenin, increases its ubiquitination, suppresses canonical Wnt/beta-catenin signaling, inhibits stem-cell self-renewal, and resensitizes cells to Osimertinib. The study also implicates a feedback loop involving Wnt signaling, Let-7d, and YTHDF3 that influences circFBXW7 translation/expression. |
| Confidence score: |
0.8035 |