| Expression pattern: |
DN |
| Associated gene: |
FGFR4, E3 ubiquitin-protein ligase CBL (c-Cbl), METTL3, YTHDF2 |
| Associated microRNA: |
- |
| Biological function: |
increases sensitivity to osimertinib; overcomes osimertinib resistance; induces apoptosis and inhibits tumor growth (especially with osimertinib) |
| Molecular mechanism: |
cLMNB1 acts as a scaffold to enhance FGFR4-c-Cbl interaction, promoting K48-linked polyubiquitination and proteasomal degradation of FGFR4; METTL3-mediated m6A and YTHDF2 promote cLMNB1 degradation |
| Biological pathway or process: |
ubiquitination (promotes); drug resistance (inhibits); apoptosis (promotes); proliferation (inhibits) |
| Detected method: |
Q
H
S
|
| Validation methods: |
circRNA-seq; RT-qPCR; Clinical Sample Validation; ISH (In Situ Hybridization); FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Luciferase Reporter Assay; Western Blot; MeRIP / MeRIP-seq; Transfection; CCK8; Annexin V/PI Flow Cytometry; In Vivo Animal Model; IHC (Immunohistochemistry); TUNEL; Bioinformatics Analysis |
| Clinical significance: |
High cLMNB1 expression was associated with delayed onset of resistance and longer progression-free survival in LUAD-OR patients. |
| Description: |
cLMNB1 is down-regulated in osimertinib-resistant LUAD and functions as a protein scaffold that promotes c-Cbl-mediated K48-linked ubiquitination and proteasomal degradation of FGFR4, thereby restoring osimertinib sensitivity. METTL3 installs m6A marks and YTHDF2 promotes cLMNB1 degradation; an m6A-site mutant (cLMNB1-mut), including LNP delivery, shows enhanced preclinical efficacy against resistance. |
| Confidence score: |
0.8875 |