| Expression pattern: |
UP |
| Associated gene: |
HIF1A, GLUT1, LDHA, PFKFB3, PKM2, HK2, AGO2 |
| Associated microRNA: |
miR-361-5p, miR-4677-3 |
| Biological function: |
promotes cetuximab resistance, cell proliferation and clonal formation; alters aerobic metabolism and glycolysis; inhibits apoptosis |
| Molecular mechanism: |
ceRNA mechanism: circHIF1A sponges miR-361-5p to upregulate HIF1A/HIF1alpha, increasing glycolysis-related enzymes (GLUT1, LDHA etc.) and glycometabolism, leading to cetuximab resistance |
| Biological pathway or process: |
ceRNA regulation (promotes); proliferation (promotes); apoptosis (inhibits); cell cycle (other); glycolysis (promotes); oxidative phosphorylation (other); drug resistance (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; FISH / smFISH; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; IF (Immunofluorescence); IHC (Immunohistochemistry); In Vivo Animal Model; Bioinformatics Analysis; Survival Analysis |
| Clinical significance: |
circHIF1A-positive patients had lower ORR/DCR and inferior PFS; circHIF1A may be a predictive indicator for cetuximab efficacy and prognosis in RAS/BRAF wild-type mCRC |
| Description: |
circHIF1A (hsa_circ_0007976), derived from HIF1A, is up-regulated in cetuximab-resistant CRC cells and promotes cetuximab resistance. It functions as a ceRNA by sponging miR-361-5p to increase HIF1A/HIF1alpha and upregulate glycolysis-related enzymes (e.g., GLUT1, LDHA), enhancing glycometabolism and tumor growth; high circHIF1A in tumors predicts worse cetuximab response and shorter PFS in RAS/BRAF wild-type mCRC. |
| Confidence score: |
0.887 |