| Expression pattern: |
UP |
| Associated gene: |
COL4A1, IGF2BP2, ACTA2, SPI1 |
| Associated microRNA: |
miR-562 |
| Biological function: |
promotes tumor-educated M2-like macrophage polarization and enhances LUAD-cell proliferation, invasion, and EMT-like changes; promotes tumor growth and metastasis |
| Molecular mechanism: |
cytoplasmic ceRNA sponging miR-562 to de-repress COL4A1; forms an RNP complex with IGF2BP2 to enhance m6A-dependent stability of COL4A1/ACTA2/SPI1 transcripts |
| Biological pathway or process: |
ceRNA regulation (promotes); m6A modification (promotes); proliferation (promotes); invasion (promotes); EMT (promotes); metastasis (promotes) |
| Detected method: |
Q
S
|
| Validation methods: |
circRNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; ISH (In Situ Hybridization); Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Transwell Assay; ELISA; Western Blot; IF (Immunofluorescence); IHC (Immunohistochemistry); In Vivo Animal Model; Survival Analysis; Bioinformatics Analysis; MeRIP / MeRIP-seq |
| Clinical significance: |
associated with advanced clinicopathological features and unfavorable survival; high circSMAD4 expression correlates with poorer overall survival |
| Description: |
In LUAD tumor-associated macrophages, circSMAD4 is up-regulated and drives a protumor, matrix-remodeling M2-like program. It acts in the cytoplasm as a ceRNA to sponge miR-562 and de-repress COL4A1, and also scaffolds the m6A reader IGF2BP2 to stabilize m6A-marked transcripts (COL4A1, ACTA2, SPI1), thereby promoting tumor growth, invasion/EMT, and metastasis. |
| Confidence score: |
0.8988 |