| Expression pattern: |
UP |
| Associated gene: |
VIRMA, AARS2, SP1, TGF-beta, Smad3 |
| Associated microRNA: |
- |
| Biological function: |
promotes proliferation; promotes migration; promotes invasion; promotes liver metastasis; promotes tumor growth; promotes EMT |
| Molecular mechanism: |
EV-delivered circTAX1BP1 binds VIRMA and recruits AARS2 to promote VIRMA K1713 lactylation, increasing VIRMA-dependent m6A modification/stability of SP1 mRNA; SP1 enhances TGF-beta transcription to activate TGF-beta/SMAD signaling and EMT, forming a positive feedback loop with ITGA11+ myCAFs (via Smad3-driven circTAX1BP1 transcription). |
| Biological pathway or process: |
m6A modification (promotes); mRNA stability (promotes); TGF-beta/SMAD (promotes); EMT (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); other pathway/process (promotes) |
| Detected method: |
Q
S
|
| Validation methods: |
RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Survival Analysis; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; ChIP / ChIP-seq; Transfection; CCK8; Colony Formation Assay; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining; Bioinformatics Analysis; MeRIP / MeRIP-seq; Western Blot |
| Clinical significance: |
High circTAX1BP1 expression is associated with liver metastasis and poorer OS/DFS in CRC; plasma EV circTAX1BP1 is upregulated in CRC and higher in LM-positive patients and shows diagnostic value (AUC 0.864). |
| Description: |
CAF/ITGA11+ myCAF-derived EV circTAX1BP1 is up-regulated in CRC/CRLM and promotes tumor growth and liver metastasis. It acts mainly by binding VIRMA and recruiting AARS2 to enhance VIRMA K1713 lactylation, which increases VIRMA-dependent m6A modification and stability of SP1 mRNA, activating SP1→TGF-beta transcription, TGF-beta/SMAD signaling, and EMT, forming a positive feedback loop in the TME. Clinically, high circTAX1BP1 indicates poor OS/DFS and plasma EV circTAX1BP1 shows diagnostic potential. |
| Confidence score: |
0.8988 |