| Expression pattern: |
UP |
| Associated gene: |
hnRNPA2B1, UBC9, ALIX, ESCRT-III, CHMP4B, PROX1 |
| Associated microRNA: |
- |
| Biological function: |
Promotes lymphangiogenesis and lymph node metastasis; enhances HLEC migration and tube formation |
| Molecular mechanism: |
circTLCD4-RWDD3 binds hnRNPA2B1 and upregulates UBC9 to promote SUMO2 modification of hnRNPA2B1 (K108), enabling SIM-dependent interaction with ALIX to recruit ESCRT-III and sort circTLCD4-RWDD3 into EVs; EV-delivered circTLCD4-RWDD3 activates PROX1 transcription in HLECs via promoter binding/DNA-RNA triplex and hnRNPA2B1-mediated H3K4me3 |
| Biological pathway or process: |
lymphangiogenesis (promotes); migration (promotes); metastasis (promotes); transcriptional regulation (promotes); other pathway/process (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; Bioinformatics Analysis; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Survival Analysis; Cohort Study; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Western Blot; IF (Immunofluorescence); ChIP / ChIP-seq; Luciferase Reporter Assay; In Vivo Animal Model; Transwell Assay; Tube Formation Assay; IHC (Immunohistochemistry); H&E Staining |
| Clinical significance: |
Higher circTLCD4-RWDD3 expression correlates with LN metastasis and is positively associated with deteriorated OS and DFS; independent predictor of OS and DFS in a multicenter cohort |
| Description: |
circTLCD4-RWDD3 is overexpressed in NSCLC (especially LN-positive cases) and enriched in NSCLC-derived extracellular vesicles, where it promotes lymphangiogenesis and lymph node metastasis. Mechanistically, it binds hnRNPA2B1 and transcriptionally upregulates UBC9 to drive hnRNPA2B1 SUMO2-K108 modification, enabling SIM-dependent ALIX activation and ESCRT-III recruitment for EV sorting; EV-delivered circTLCD4-RWDD3 activates PROX1 transcription in HLECs to enhance lymphangiogenic phenotypes and metastasis. |
| Confidence score: |
0.9031 |