| Expression pattern: |
UP |
| Associated gene: |
IGF2BP3, METTL3, ASS1 |
| Associated microRNA: |
- |
| Biological function: |
promotes stemness properties, proliferation, and tumorigenicity; reduces sorafenib sensitivity |
| Molecular mechanism: |
METTL3-mediated m6A modification enables IGF2BP3 binding to circRAPGEF1 to stabilize it; circRAPGEF1 competitively binds IGF2BP3 to disrupt IGF2BP3/ASS1 mRNA interaction, destabilizing ASS1 mRNA and activating S6K/CAD signaling via aspartate accumulation |
| Biological pathway or process: |
stemness (promotes); proliferation (promotes); m6A modification (other); mRNA stability (inhibits); other pathway/process (promotes); drug resistance (promotes) |
| Detected method: |
Q
S
M
|
| Validation methods: |
Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; Clinical Sample Validation; Survival Analysis; Transfection; CCK8; EdU Staining; Colony Formation Assay; Western Blot; IHC (Immunohistochemistry); RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; RNA-seq; In Vivo Animal Model; Bioinformatics Analysis |
| Clinical significance: |
upregulated in HCC tissues and predictive of poor patient survival |
| Description: |
circRAPGEF1 is upregulated in HCC/LCSCs and promotes stemness, proliferation, and tumorigenicity while decreasing sorafenib sensitivity. METTL3 installs m6A on circRAPGEF1 enabling IGF2BP3 binding to stabilize it; circRAPGEF1 then competitively sequesters IGF2BP3 from ASS1 mRNA, destabilizing ASS1, increasing aspartate and activating S6K/CAD signaling to drive HCC progression. |
| Confidence score: |
0.8939 |