circRNA basic information
circBase ID: hsa_circ_0082002
Name: hsa_circ_MET
Synonym: circMET
Host Gene: MET
Genomic location(hg19): chr7:116339124-116340338:+
Genomic location(hg38): chr7:116699070-116700284:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0019056
MONDO name: neuromuscular disease
Disease details: ocular vascular dysfunction
Disease DO ID:
440
Disease MeSH ID:
D009468
Disease NCIt ID:
-
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

retinas; choroidal tissues; retinal vessels; vitreous samples; RPE/choroid complexes

Cell lines:

HRVECs

In vivo animal model:

genetically engineered animal model; other disease animal model

circRNA-disease information
Expression pattern:
UP
Associated gene: IGF2BP2, IGF2BP1, IGF2BP3, NRARP, ESM1, METTL3, METTL14
Associated microRNA: -
Biological function: Promotes endothelial tip cell specialization, endothelial migration and sprouting, retinal and choroidal pathological angiogenesis, retinal vascular leakage, and neovascular tuft formation.
Molecular mechanism: Acts as an m6A-dependent scaffold that interacts with IGF2BP2 and promotes formation of circMET/IGF2BP2/NRARP or ESM1 complex, thereby stabilizing NRARP and ESM1 mRNAs; it does not act as a miRNA sponge in HRVECs.
Biological pathway or process:

angiogenesis (promotes); migration (promotes); mRNA stability (promotes); m6A modification (other); Notch (other); Wnt/beta-catenin (other); VEGF/VEGFR (promotes); other pathway/process (promotes)

Detected method:
Q
Validation methods:

RT-qPCR; FISH / smFISH; IF (Immunofluorescence); Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; MeRIP / MeRIP-seq; Transfection; Transwell Assay; Western Blot; ELISA; In Vivo Animal Model; Bioinformatics Analysis

Clinical significance:

circMET is upregulated in vitreous samples of patients with DME or PDR, correlates with severity of retinal vascular dysfunction, is reduced by anti-VEGF treatment, and is proposed as a diagnostic/prognostic biomarker and therapeutic target for ocular vascular disease.

Description:

circMET is upregulated in mouse models of ocular pathological angiogenesis and in vitreous samples from patients with diabetic retinal vascular disease. It promotes endothelial tip cell specialization, endothelial sprouting, migration, and pathological angiogenesis by forming an m6A-dependent circMET/IGF2BP2/NRARP or ESM1 complex that stabilizes NRARP and ESM1 expression. The study proposes circMET as a biomarker and therapeutic target for proliferative retinopathies and other neovascular diseases.

Confidence score:

0.7519

Other information
Title:

Targeting circular RNA-MET for anti-angiogenesis treatment via inhibiting endothelial tip cell specialization.

Journal: Molecular therapy : the journal of the American Society of Gene Therapy
Published: 2022
PubMed ID: 34999209
Study type:

combined biological and clinical study

Data availability: Table S1; Supplemental information: https://doi.org/10. 1016/j.ymthe.2022.01.012
Code availability: -