| Expression pattern: |
UP |
| Associated gene: |
METTL3, EIF4A3, YAP1 |
| Associated microRNA: |
- |
| Biological function: |
promotes osimertinib resistance, cell proliferation, and survival; inhibits apoptosis; enhances tumor growth in vivo |
| Molecular mechanism: |
METTL3-dependent m6A modification increases circKRT17 stability; circKRT17 recruits EIF4A3 to enhance YAP1 mRNA stability and promotes YAP1 nuclear transport, activating YAP1 signaling |
| Biological pathway or process: |
Hippo/YAP (promotes); proliferation (promotes); apoptosis (inhibits); drug resistance (promotes); m6A modification (promotes) |
| Detected method: |
Q
M
|
| Validation methods: |
RT-qPCR; Microarray; RNase R Treatment; Actinomycin D / DRB Stability Assay; Sanger Sequencing; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; MeRIP / MeRIP-seq; RNA Pull-Down; RIP (RNA Immunoprecipitation); Transfection; MTT; Colony Formation Assay; EdU Staining; Annexin V/PI Flow Cytometry; Western Blot; In Vivo Animal Model; IHC (Immunohistochemistry); TUNEL; Bioinformatics Analysis |
| Clinical significance: |
circKRT17 may act as a biomarker of osimertinib resistance of LUAD |
| Description: |
circKRT17 is up-regulated in osimertinib-insensitive LUAD tissues and resistant cell lines and promotes osimertinib resistance. Mechanistically, METTL3-mediated m6A modification stabilizes circKRT17, which recruits EIF4A3 to increase YAP1 mRNA stability and enhance YAP1 nuclear localization/activation, supporting tumor growth and survival under osimertinib. |
| Confidence score: |
0.8519 |