| Expression pattern: |
DN |
| Associated gene: |
HNRNPL, CCL5 mRNA |
| Associated microRNA: |
- |
| Biological function: |
Acts as a tumor-suppressing circRNA that enhances CCL5 expression and secretion, recruits CD8+ T cells, promotes immune killing of bladder cancer cells, suppresses xenograft tumor growth, and potentiates anti-PD-1 immunotherapy. |
| Molecular mechanism: |
circMGA interacts with HNRNPL in the cytoplasm, promotes HNRNPL binding to CCL5 mRNA 3′-UTR, stabilizes CCL5 mRNA, increases CCL5 expression and secretion, and recruits CD8+ T cells; HNRNPL also stabilizes circMGA, forming a positive feedback loop. |
| Biological pathway or process: |
mRNA stability (promotes); immune regulation (promotes); apoptosis (promotes); proliferation (inhibits); drug resistance (other); other pathway/process (promotes) |
| Detected method: |
Q
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; Flow Cytometry(Non-apoptosis/cycle); Transwell Assay; TUNEL; In Vivo Animal Model; IHC (Immunohistochemistry); ELISA; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis |
| Clinical significance: |
circMGA is downregulated in bladder cancer, negatively associated with pathological stage and grade, and low circMGA expression is associated with poor overall survival; circMGA may be a target for combination immunotherapy with PD-1 checkpoint blockade. |
| Description: |
circMGA is a human MGA-derived circRNA that is downregulated in bladder cancer and whose higher expression is associated with favorable overall survival. It acts as a cytoplasmic tumor suppressor by binding HNRNPL, stabilizing CCL5 mRNA, increasing CCL5 secretion, recruiting CD8+ T cells, and enhancing anti-PD-1 immunotherapy efficacy. |
| Confidence score: |
0.8981 |