| Expression pattern: |
UP |
| Associated gene: |
IGF1R, CDC42 |
| Associated microRNA: |
miR-512-5p |
| Biological function: |
Promotes osimertinib resistance, promotes proliferation/viability and inhibits apoptosis in osimertinib-resistant LUAD cells; promotes xenograft tumor growth and reduces sensitivity to osimertinib. |
| Molecular mechanism: |
Acts as a ceRNA/miRNA sponge for miR-512-5p to de-repress IGF1R, activating downstream IGF1R signaling with increased AKT and ERK1/2 phosphorylation, promoting osimertinib resistance. |
| Biological pathway or process: |
PI3K/AKT (promotes); MAPK (promotes); ERK (promotes); proliferation (promotes); apoptosis (inhibits); drug resistance (promotes); ceRNA regulation (promotes) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; Transfection; RNA Pull-Down; Luciferase Reporter Assay; MTT; Colony Formation Assay; Annexin V/PI Flow Cytometry; Western Blot; In Vivo Animal Model |
| Clinical significance: |
May serve as a diagnostic indicator for monitoring osimertinib resistance and a potential therapeutic target in LUAD. |
| Description: |
hsa_circ_0005576 is up-regulated in osimertinib-resistant LUAD cell models and promotes resistance by enhancing proliferation/viability and suppressing apoptosis. It functions as a miRNA sponge for miR-512-5p, thereby upregulating IGF1R and activating downstream AKT and ERK signaling; knockdown sensitizes resistant cells and xenografts to osimertinib. |
| Confidence score: |
0.7746 |