circRNA basic information
circBase ID: hsa_circ_0006990
Name: hsa_circ_VAPA
Synonym: circVAPA
Host Gene: VAPA
Genomic location(hg19): chr18:9931806-9937063:+
Genomic location(hg38): chr18:9931809-9937066:+
Subcellular localization: cytoplasm; extracellular vesicle
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0001056
MONDO name: gastric cancer
Disease details: gastric cancer
Disease DO ID:
10534
Disease MeSH ID:
-
Disease NCIt ID:
C9331
Disease ICD11 ID:
1397617262
Disease OMIM ID:
613659
Species: Human
Species details: Homo sapiens
Tissue specimen:

plasma sEVs; serum samples; GC tissue; adjacent tissues; GC tissues; tissue sEVs

Cell lines:

AGS; HGC27; SH-SY5Y; MKN28; MKN45; HEK293

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: SLIT2, TGIF2, eIF4G1, eIF4E, eIF4F complex
Associated microRNA: miR-548p
Biological function: Promotes gastric cancer neural invasion in vitro and in vivo; enhances neuritogenesis of dorsal root ganglia and neuronal-cell-dependent migration of gastric cancer cells; downregulates SLIT2 expression in neuronal cells.
Molecular mechanism: sEV-circVAPA acts through both miRNA sponge and protein-binding mechanisms: it sponges miR-548p to elevate TGIF2 and repress SLIT2 transcription, and binds eIF4G1 to disrupt eIF4G1/eIF4E interaction and suppress SLIT2 translation.
Biological pathway or process:

invasion (promotes); migration (promotes); ceRNA regulation (other); other pathway/process (other)

Detected method:
Q
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; Transwell Assay; In Vivo Animal Model; H&E Staining; Western Blot; Cohort Study; Survival Analysis; ROC Analysis; Bioinformatics Analysis; IF (Immunofluorescence)

Clinical significance:

circVAPA in plasma sEVs and GC tissues may serve as a biomarker for GC neural invasion; higher circVAPA expression in GC tissues predicts poor overall survival.

Description:

hsa_circ_0006990/circVAPA is enriched in plasma small extracellular vesicles and tumor tissues from NI-positive gastric cancer patients and is associated with poor overall survival. Functionally, GC-derived sEV-circVAPA promotes gastric cancer neural invasion by entering neuronal cells, suppressing SLIT2 transcription through the miR-548p/TGIF2 axis, and inhibiting SLIT2 translation through eIF4G1 binding and disruption of the eIF4F complex.

Confidence score:

0.9045

Other information
Title:

circVAPA-rich small extracellular vesicles derived from gastric cancer promote neural invasion by inhibiting SLIT2 expression in neuronal cells.

Journal: Cancer letters
Published: 2024
PubMed ID: 38714291
Study type:

combined biological and clinical study

Data availability: Supplementary data; https://doi.org/10.1016/j.canlet.2024.216926; data available from corresponding authors upon reasonable request
Code availability: -