| Expression pattern: |
UP |
| Associated gene: |
circPICALM-219aa, METTL3, YTHDC1, DDX3, STAT3, SOCS3, JAK2, IL-6 |
| Associated microRNA: |
- |
| Biological function: |
Promotes ICC cell migration, invasion, intrahepatic metastasis, and lung metastasis; encodes the metastasis-promoting protein circPICALM-219aa; does not significantly affect proliferation, cell cycle progression, or apoptosis. |
| Molecular mechanism: |
METTL3-mediated m6A modification and YTHDC1-mediated back-splicing promote circPICALM biogenesis; DDX3 binds the IRES element to enhance circPICALM-219aa translation; circPICALM-219aa binds STAT3 and SOCS3, disrupts SOCS3-mediated inhibition of JAK2/STAT3, and amplifies IL-6/JAK/STAT3 signaling. |
| Biological pathway or process: |
JAK/STAT (promotes); migration (promotes); invasion (promotes); metastasis (promotes); m6A modification (other); other pathway/process (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; Actinomycin D / DRB Stability Assay; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); Co-IP; IHC (Immunohistochemistry); IF (Immunofluorescence); Luciferase Reporter Assay; MeRIP / MeRIP-seq; Transfection; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis; RNA-seq |
| Clinical significance: |
High circPICALM expression is associated with metastasis, aggressive clinicopathological features, earlier recurrence, shorter overall survival and recurrence-free survival, and is an independent risk factor for poor OS and RFS in ICC patients after hepatectomy. |
| Description: |
circPICALM is a human PICALM-derived circRNA that is upregulated in recurrent and metastatic ICC and predicts poor OS and RFS. Its m6A/YTHDC1-dependent biogenesis and DDX3-regulated IRES-dependent translation produce circPICALM-219aa, which promotes ICC migration, invasion, and metastasis by antagonizing SOCS3 and sustaining IL-6/JAK/STAT3 signaling. |
| Confidence score: |
0.9032 |