| Expression pattern: |
UP |
| Associated gene: |
Rab5B, CD109, TRPV1, DSCAML1, GFRalpha1, RET, FLOT1 |
| Associated microRNA: |
- |
| Biological function: |
promotes axonogenesis and perineural invasion (PNI) in KRASG12D-mutant PDAC; facilitates neural metastasis/neurotropism |
| Molecular mechanism: |
circPNIT acts as a scaffold to link Rab5B and CD109, enabling lipid-raft/MVB-associated EV packaging and CD109+ EV secretion; CD109+ EVs target neurons via TRPV1 and circPNIT activates DSCAML1 transcription (via promoter binding and increased H3K9Ac), inducing axonogenesis and activating GFRalpha1/RET with downstream MAPK/ERK signaling |
| Biological pathway or process: |
axonogenesis (promotes); metastasis (promotes); MAPK (promotes); ERK (promotes); other pathway/process (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
RNA-seq; 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; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Luciferase Reporter Assay; ChIP / ChIP-seq; Transfection; Transwell Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); ISH (In Situ Hybridization); Flow Cytometry（Non-apoptosis/cycle）; Western Blot; Bioinformatics Analysis |
| Clinical significance: |
Positively correlated with PNI severity and nerve density; high tissue/serum EV circPNIT predicts shorter OS and DFS and is an independent predictor of poor survival; potential diagnostic and predictive value for neuroinvasive KRASG12D PDAC |
| Description: |
circPNIT (hsa_circ_0007006), a DYM-derived circRNA, is upregulated in KRASG12D PDAC tissues and serum EVs and correlates with PNI severity and poor survival. It scaffolds Rab5B and CD109 to promote lipid-raft/MVB-dependent loading into CD109+ EVs, which target neurons via TRPV1; in neurons, circPNIT enhances DSCAML1 transcription (with increased H3K9Ac), promotes axonogenesis, and activates the GFRalpha1/RET→MAPK/ERK signaling that facilitates PNI. |
| Confidence score: |
0.8993 |