| Expression pattern: |
DN |
| Associated gene: |
SEMA3C-319aa, LDHA, GPX4, PARK2, HIF-1alpha, importin beta1 |
| Associated microRNA: |
- |
| Biological function: |
Suppresses GC cell viability, proliferation and tumor growth, promotes cell death, and enhances ferroptosis sensitivity through its encoded protein SEMA3C-319aa. |
| Molecular mechanism: |
circSEMA3C encodes SEMA3C-319aa; SEMA3C-319aa binds LDHA and promotes LDHA nuclear translocation via a non-canonical NLS/importin beta1 mechanism; nuclear LDHA promotes PARK2 transcription via HIF-1alpha, leading to K48-linked ubiquitination and degradation of GPX4, reduced GSH metabolism, and ferroptosis. |
| Biological pathway or process: |
ferroptosis (promotes); proliferation (inhibits); ubiquitination (promotes); lipid metabolism (promotes); other pathway/process (inhibits) |
| Detected method: |
Q
S
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; RNA-seq; circRNA-seq; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Co-IP; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); IF (Immunofluorescence); Western Blot; ROC Analysis; Bioinformatics Analysis |
| Clinical significance: |
circSEMA3C is downregulated in GC tissues, lower in stage III-IV tumors and lymph node metastasis, and may serve as a diagnostic and prognostic biomarker; ROC AUC for distinguishing GC cases with and without lymph node metastasis was 0.7333. |
| Description: |
circSEMA3C is a human SEMA3C-derived circRNA that is downregulated in gastric cancer and encodes the novel protein SEMA3C-319aa. The circSEMA3C/SEMA3C-319aa axis suppresses GC cell proliferation and tumor growth by promoting GSH metabolism-dependent ferroptosis through LDHA nuclear translocation, PARK2-mediated K48-linked GPX4 ubiquitination, and GPX4 degradation. Its reduced expression is associated with advanced stage and lymph node metastasis, and SEMA3C-319aa may improve response to GPX4 inhibition. |
| Confidence score: |
0.8837 |