circRNA basic information
circBase ID: hsa_circ_0000817
Name: hsa_circ_FOXK2
Synonym: circ-FOXK2
Host Gene: FOXK2
Genomic location(hg19): chr17:80521229-80529746:+
Genomic location(hg38): chr17:82563353-82571870:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005061
MONDO name: lung adenocarcinoma
Disease details: advanced lung adenocarcinoma
Disease DO ID:
3910
Disease MeSH ID:
C538231
Disease NCIt ID:
C3512
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

advanced LUAD tissues; tumor tissues; adjacent non-tumor tissues; paraffin-embedded LUAD tissue specimens; fresh tissue samples; metastatic sites; primary tumors

Cell lines:

PC9; H1975; H460; H1650; A549; SPC-A1; H23; H1299; H2228; BEAS-2B; HUVEC

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: CLDN1, bevacizumab
Associated microRNA: miR-1275
Biological function: circFOXK2 inhibits vascular permeability and angiogenesis; reduced circFOXK2 promotes vascular permeability, endothelial migration, angiogenesis, vascular sprouting, tumor growth and angiogenesis; circFOXK2 overexpression synergizes with bevacizumab to suppress vascular permeability and angiogenesis.
Molecular mechanism: Low circFOXK2 expression upregulates miR-1275 in tumor cells; miR-1275 is transferred to endothelial cells via exosomes and targets CLDN1, reducing tight junction protein expression to enhance vascular permeability and angiogenesis.
Biological pathway or process:

angiogenesis (inhibits); migration (inhibits); metastasis (inhibits); ceRNA regulation (other); drug resistance (other); other pathway/process (inhibits)

Detected method:
Q
H
M
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; Microarray; FISH / smFISH; ISH (In Situ Hybridization); IHC (Immunohistochemistry); IF (Immunofluorescence); Clinical Sample Validation; Luciferase Reporter Assay; Transfection; Transwell Assay; Tube Formation Assay; In Vivo Animal Model; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis

Clinical significance:

Low circFOXK2 expression is associated with poor prognosis and is an independent predictor of overall survival; circFOXK2 expression correlates with T classification and distant metastasis; circFOXK2 is positioned as a potential diagnostic and therapeutic biomarker for advanced LUAD.

Description:

circFOXK2 is down-regulated in advanced LUAD tissues, especially in highly angiogenic tumors, and low expression is associated with poor prognosis. Mechanistically, reduced circFOXK2 increases miR-1275, which is transferred via exosomes to endothelial cells and suppresses CLDN1, thereby enhancing vascular permeability and angiogenesis. circFOXK2 overexpression also synergizes with bevacizumab to inhibit angiogenesis and tumor growth, suggesting therapeutic potential.

Confidence score:

0.8645

Other information
Title:

circFOXK2 inhibits vascular permeability and angiogenesis in advanced lung adenocarcinoma via the miR-1275/CLDN1 axis.

Journal: Biochemical and biophysical research communications
Published: 2025
PubMed ID: 40850182
Study type:

combined biological and clinical study

Data availability: GSE289070; supplementary materials; Supplemental Excel file 1; https://doi.org/10.1016/j.bbrc.2025.152517
Code availability: -