| Expression pattern: |
UP |
| Associated gene: |
IGF2BP3, c-Myc mRNA, c-Myc, CXCL10, IL-9, IFN-g, JAK1, JAK2, STAT1, CD8 + T cells |
| Associated microRNA: |
- |
| Biological function: |
circDNA2v maintains the oncogenic phenotype of CRC cells, prevents cellular senescence and cell-cycle arrest, promotes proliferation and clonogenicity, and its silencing induces a proinflammatory SASP that recruits and activates CD8 + T cells. |
| Molecular mechanism: |
circDNA2v directly binds IGF2BP3, prevents IGF2BP3 ubiquitination and proteasomal degradation, facilitates IGF2BP3 binding to c-Myc mRNA, and stabilizes c-Myc mRNA. circDNA2v silencing activates IFN-g/JAK-STAT1 signaling to enhance CXCL10 and IL-9 secretion. |
| Biological pathway or process: |
proliferation (promotes); cell cycle (promotes); mRNA stability (promotes); ubiquitination (inhibits); JAK/STAT (inhibits); immune regulation (inhibits); other pathway/process (inhibits) |
| Detected method: |
Q
B
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; Northern Blot; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Transfection; EdU Staining; Colony Formation Assay; Cell Cycle Assay; Transwell Assay; In Vivo Animal Model; IHC (Immunohistochemistry); IF (Immunofluorescence); ELISA; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis; Flow Cytometry(Non-apoptosis/cycle) |
| Clinical significance: |
High circDNA2v expression in CRC tumors is associated with significantly shorter overall survival and lower intratumoral CD8 + T cell infiltration. |
| Description: |
circDNA2v is a DNA2-derived human circRNA upregulated in colorectal cancer and associated with poor overall survival. Mechanistically, it binds IGF2BP3, protects IGF2BP3 from ubiquitin-mediated degradation, and stabilizes c-Myc mRNA to maintain CRC cell proliferation and prevent senescence. Silencing circDNA2v induces senescence and a JAK-STAT1-dependent SASP enriched for CXCL10 and IL-9, promoting CD8 + T cell recruitment and cytotoxicity. |
| Confidence score: |
0.8898 |