| Expression pattern: |
UP |
| Associated gene: |
LDHA, SIRT2, HSC70, LAMP2A |
| Associated microRNA: |
- |
| Biological function: |
promotes lactate metabolic reprogramming (Warburg effect), suppresses NK cell cytotoxicity (innate immune evasion), promotes proliferation, migration/invasion and metastasis of HCC |
| Molecular mechanism: |
circSMPD4 physically binds LDHA and acts as a scaffold to enhance SIRT2-LDHA interaction, reducing LDHA acetylation; this inhibits LDHA-HSC70 binding and prevents LDHA degradation via chaperone-mediated autophagy (CMA) lysosome pathway, increasing lactate production/export and suppressing NK cell function |
| Biological pathway or process: |
glycolysis (promotes); immune regulation (inhibits); metastasis (promotes); proliferation (promotes); migration (promotes); invasion (promotes); mitochondrial function (other); autophagy (inhibits); other pathway/process (other) |
| Detected method: |
Q
M
|
| Validation methods: |
Microarray; 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; Cohort Study; Survival Analysis; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; Transwell Assay; In Vivo Animal Model; IF (Immunofluorescence); Co-IP; Western Blot |
| Clinical significance: |
Elevated circSMPD4 expression in tumor tissues was significantly associated with reduced overall survival and shortened disease‐free survival in HCC patients. |
| Description: |
circSMPD4 is upregulated in HCC and promotes Warburg-like lactate production, leading to reduced NK-cell cytotoxicity and enhanced immune evasion, tumor growth, and metastasis. It binds LDHA and scaffolds SIRT2 to deacetylate LDHA, blocking LDHA-HSC70 engagement and CMA-lysosomal degradation, thereby stabilizing LDHA and increasing lactate export. |
| Confidence score: |
0.8893 |