| Expression pattern: |
UP |
| Associated gene: |
PKM2, ALDOA, ELAVL1/HuR, Norathyriol |
| Associated microRNA: |
- |
| Biological function: |
promotes glycolysis and metastasis; increases PKM2 kinase activity and ALDOA-S36 phosphorylation; impairs anti-HCC immunity by increasing HuR-dependent SLC43A2 mRNA stability and inducing methionine/leucine deficiency in CD8+ T cells; contributes to resistance to anti-PD1 therapy |
| Molecular mechanism: |
m6A-driven translation from circPETH; circPETH-147aa binds PKM2 and ALDOA to enhance PKM2-catalyzed ALDOA-S36 phosphorylation via MEG pocket; binds HuR via MEG pocket to sustain HuR S100 phosphorylation, strengthening HuR binding to SLC43A2 mRNA and increasing mRNA stability |
| Biological pathway or process: |
glycolysis (promotes); metastasis (promotes); migration (promotes); invasion (promotes); immune regulation (inhibits); m6A modification (promotes); mRNA stability (promotes); Hippo/YAP (inhibits) |
| Detected method: |
Others
|
| Validation methods: |
Transfection; Western Blot; Mass spectrometry (MS); IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Co-IP; RIP (RNA Immunoprecipitation); MeRIP / MeRIP-seq; Luciferase Reporter Assay; RNA-seq; Bioinformatics Analysis; Actinomycin D / DRB Stability Assay; Transwell Assay; Annexin V/PI Flow Cytometry; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; H&E Staining; SPR; CCK8 |
| Clinical significance: |
Norathyriol inhibits circPETH-147aa by targeting the MEG pocket and reverses circPETH-147aa-driven malignant phenotypes; norathyriol increases anti-PD1 efficacy by restoring CD8+ T-cell function |
| Description: |
circPETH-147aa is an m6A-driven translation product of circPETH that directly binds PKM2/ALDOA and boosts PKM2 kinase activity to promote ALDOA-S36 phosphorylation via its MEG pocket, enhancing glycolysis and metastatic traits in HCC cells. It also binds HuR to increase SLC43A2 mRNA stability, elevating methionine/leucine uptake by tumor cells and suppressing CD8+ T-cell cytotoxicity; norathyriol blocks this by targeting the MEG pocket and improves anti-PD1 efficacy. |
| Confidence score: |
0.7596 |