circRNA basic information
circBase ID: hsa_circ_0039992
Name: hsa_circ_CDH1
Synonym: circ-E-Cad RNA
Host Gene: -
Genomic location(hg19): chr16:68845586-68849662:+
Genomic location(hg38): chr16:68811683-68815759:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0018177
MONDO name: glioblastoma
Disease details: glioblastoma
Disease DO ID:
 3068
Disease MeSH ID:
 D005909
Disease NCIt ID:
 C3058
Disease ICD11 ID:
 -
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

GBM specimens; paired normal brain tissues; primary GBM tissues; NB tissues
Cell lines:

GSC456; GSC4121; GSC3691; GSCH2S; GSC387; GSC17; GSC23; NSCs; NHAs; HEK293T; iPSC-derived NSCs
In vivo animal model:

patient-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: C-E-Cad, EGFR, EGFRvIII, STAT3, AKT, ERK1/2
Associated microRNA: -
Biological function: circ-E-Cad RNA encodes C-E-Cad, an oncogenic E-cadherin variant that promotes GSC stemness, sphere formation, proliferation, invasion, apoptosis resistance, senescence resistance and intracranial tumorigenicity.
Molecular mechanism: circ-E-Cad RNA is translated into C-E-Cad; secreted C-E-Cad directly binds the CR2 domain of EGFR through its unique C-terminal 14-aa sequence and persistently activates EGFR-STAT3, PI3K-AKT and MAPK-ERK signalling.
Biological pathway or process:

EGFR (promotes); JAK/STAT (promotes); PI3K/AKT (promotes); MAPK (promotes); ERK (promotes); proliferation (promotes); invasion (promotes); apoptosis (inhibits); stemness (promotes); drug resistance (promotes); other pathway/process (promotes)
Detected method:
Q
B
H
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; RT-qPCR; RNA-seq; Northern Blot; FISH / smFISH; IHC (Immunohistochemistry); IF (Immunofluorescence); Clinical Sample Validation; RNA Pull-Down; Co-IP; Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; In Vivo Animal Model; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis
Clinical significance:

C-E-Cad/circ-E-Cad is an independent prognostic factor in GBM; C-E-Cad expression inversely correlates with overall survival, and targeting C-E-Cad may enhance anti-EGFR therapy.
Description:

circ-E-Cad RNA, a CDH1-derived circRNA annotated as hsa_circ_0039992, is up-regulated in GBM and GSCs and encodes the secreted oncogenic protein C-E-Cad. C-E-Cad directly binds EGFR/EGFRvIII through its unique C-terminal sequence and activates EGFR-STAT3, PI3K-AKT and MAPK-ERK signalling to promote stemness, proliferation, invasion, survival and intracranial tumorigenicity. High C-E-Cad expression is associated with poor overall survival, and anti-C-E-Cad antibody treatment enhances anti-EGFR therapeutic effects in GBM xenografts.
Confidence score:

0.8978
Other information
Title:

Circular RNA-encoded oncogenic E-cadherin variant promotes glioblastoma tumorigenicity through activation of EGFR-STAT3 signalling.

Journal: Nature cell biology
Published: 2021
PubMed ID: 33664496
Study type:

combined biological and clinical study
Data availability: PRJNA525736; SRA714646; TCGA; CGGA 301 dataset; http://gepia.cancer-pku.cn/detail.php?gene; http://www.cgga.org.cn/download.jsp; Supplementary Table 1; Supplementary Table 2; Supplementary Table 3; Supplementary Table 11; Supplementary Table 13
Code availability: -