| Expression pattern: |
UP |
| Associated gene: |
EGFR, rtEGFR |
| Associated microRNA: |
- |
| Biological function: |
circ-EGFR encodes rtEGFR, sustains EGFR activation and membrane localization, promotes BTIC/GBM proliferation, stemness and tumorigenicity, predicts poor prognosis, and its knockdown enhances the anti-GBM effect of nimotuzumab. |
| Molecular mechanism: |
circ-EGFR contains an infinite open reading frame that undergoes rolling translation and programmed -1 ribosomal frameshifting to produce rtEGFR; rtEGFR directly binds EGFR, maintains EGFR membrane localization, attenuates EGFR endocytosis, ubiquitination and degradation, and sustains EGFR downstream signaling. |
| Biological pathway or process: |
EGFR (promotes); PI3K/AKT (promotes); ERK (promotes); JAK/STAT (promotes); proliferation (promotes); stemness (promotes); drug resistance (promotes); ubiquitination (inhibits); other pathway/process (promotes) |
| Detected method: |
Q
B
S
|
| Validation methods: |
RNase R Treatment; Sanger Sequencing; RNA-seq; Northern Blot; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RT-qPCR; Clinical Sample Validation; IF (Immunofluorescence); Co-IP; Transfection; CCK8; Colony Formation Assay; In Vivo Animal Model; H&E Staining; Western Blot; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
circ-EGFR levels correlated with the EGFR signature and predicted poor prognosis of GBM patients; targeting rtEGFR may improve EGFR-targeting therapies in GBM. |
| Description: |
circ-EGFR is up-regulated in GBM/BTICs and is derived from exons 14 and 15 of EGFR. It encodes the rolling-translated protein rtEGFR, which binds EGFR, preserves EGFR membrane localization, reduces EGFR endocytosis/ubiquitination/degradation, and sustains EGFR downstream signaling. High circ-EGFR predicts poor overall survival in GBM patients, while circ-EGFR knockdown reduces tumorigenicity and sensitizes tumors to nimotuzumab. |
| Confidence score: |
0.83 |