| Expression pattern: |
UP |
| Associated gene: |
PDGFB, MAPK pathway, RAF/MEK/ERK cascade, AGO2, RISC |
| Associated microRNA: |
miR-625-5p |
| Biological function: |
enhances cell survival, proliferation, and invasion; suppresses apoptosis; promotes osimertinib resistance; circROBO2 knockdown partially restores osimertinib sensitivity |
| Molecular mechanism: |
circROBO2 acts as a ceRNA/molecular sponge for miR-625-5p, increasing PDGFB expression and activating the MAPK pathway, particularly the RAF/MEK/ERK cascade, to promote osimertinib resistance |
| Biological pathway or process: |
MAPK (promotes); ERK (promotes); proliferation (promotes); invasion (promotes); apoptosis (inhibits); drug resistance (promotes); ceRNA regulation (other) |
| Detected method: |
Q
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; RNA-seq; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; Transwell Assay; Western Blot; Bioinformatics Analysis |
| Clinical significance: |
potential therapeutic target and biomarker for NSCLC treatment and osimertinib resistance |
| Description: |
circROBO2 (hsa_circ_0066556), derived from ROBO2, is up-regulated in osimertinib-resistant NSCLC cells. It promotes osimertinib resistance by sponging miR-625-5p, increasing PDGFB expression, and activating the MAPK/RAF/MEK/ERK pathway, thereby enhancing survival, proliferation, and invasion while reducing apoptosis. The study proposes circROBO2 as a potential biomarker and therapeutic target for osimertinib resistance in NSCLC. |
| Confidence score: |
0.7961 |