| Expression pattern: |
DN |
| Associated gene: |
TPM4 mRNA, TPM4 pre-mRNA, YBX1, hnRNPA1, hnRNPD, hnRNPK, UPF1, DHX9 |
| Associated microRNA: |
- |
| Biological function: |
Suppresses HCC metastasis by impairing cytoskeleton assembly, reducing cell adhesion, migration and invasion; promotes decay of TPM4 transcripts. |
| Molecular mechanism: |
Acts as a nuclear scaffold that binds TPM4 mRNA/pre-mRNA and promotes YBX1 liquid-liquid phase separation, assembling a YBX1/hnRNP complex to alter TPM4 transcript splicing and trigger nonsense-mediated decay, leading to TPM4 repression. |
| Biological pathway or process: |
metastasis (inhibits); migration (inhibits); invasion (inhibits); proliferation (other); PI3K/AKT (inhibits); ceRNA regulation (inhibits); other pathway/process (other) |
| Detected method: |
Q
H
M
|
| Validation methods: |
Microarray; RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Survival Analysis; Actinomycin D / DRB Stability Assay; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; Western Blot; IF (Immunofluorescence); Transwell Assay; In Vivo Animal Model; H&E Staining; Bioinformatics Analysis |
| Clinical significance: |
Down-regulated circASH2 expression indicates worse prognosis; lower circASH2 in tumors correlates with shortened overall survival and disease-free survival. |
| Description: |
circASH2 is down-regulated in HCC and acts as a nuclear tumor-suppressive circRNA that inhibits metastasis by impairing cytoskeleton/adhesion. It binds TPM4 transcripts and promotes YBX1 LLPS to assemble a YBX1/hnRNP complex, driving splicing-coupled NMD and decay of TPM4, thereby suppressing FAK/PI3K/AKT-associated motility programs. |
| Confidence score: |
0.8778 |