| Expression pattern: |
UP |
| Associated gene: |
YTHDF2, GADD45A |
| Associated microRNA: |
- |
| Biological function: |
Promotes PM2.5-induced malignant transformation (proliferation/colony formation, migration, invasion, tumor growth and metastasis) by inhibiting GADD45A. |
| Molecular mechanism: |
circDNA2 binds the YTHDF2 LC domain, promotes YTHDF2 liquid-liquid phase separation, and enhances YTHDF2-mediated m6A-dependent degradation/blunting of GADD45A mRNA. |
| Biological pathway or process: |
LLPS (promotes); m6A modification (promotes); mRNA stability (inhibits); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
circRNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Transfection; RNA Pull-Down; RIP (RNA Immunoprecipitation); RNA-seq; Bioinformatics Analysis; Luciferase Reporter Assay; Western Blot; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; ISH (In Situ Hybridization); IHC (Immunohistochemistry); Survival Analysis; ROC Analysis; Cohort Study; Clinical Sample Validation |
| Clinical significance: |
Increased circDNA2 expression in lung cancer tissues is associated with decreased overall survival; circDNA2 is evaluated as a potential prognostic biomarker. |
| Description: |
circDNA2 is upregulated after chronic PM2.5 exposure and in lung cancer tissues, and it promotes malignant transformation phenotypes. Mechanistically, circDNA2 binds the LC domain of YTHDF2 to enhance YTHDF2 LLPS and thereby blunts GADD45A expression via an m6A-dependent, YTHDF2-mediated post-transcriptional mechanism. High circDNA2 expression is associated with worse overall survival, supporting its prognostic value in lung cancer. |
| Confidence score: |
0.9 |