circRNA basic information
circBase ID: hsa_circ_0008450
Name: hsa_circ_CMTM3
Synonym: circCMTM3
Host Gene: CMTM3
Genomic location(hg19): chr16:66642211-66643906:+
Genomic location(hg38): chr16:66608308-66610003:+
Subcellular localization: cytoplasm; exosome
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0018177
MONDO name: glioblastoma
Disease details: glioblastoma / GBM
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:

glioma tissues-derived exosomes; normal brain tissue-derived exosomes
Cell lines:

GSC01; GSC03; DGC01; DGC03
In vivo animal model:

patient-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: CNOT4, STAT5A, STAT5B, JAK2, CHI3L2, SRSF1
Associated microRNA: -
Biological function: Promotes vasculogenic mimicry formation and accelerates malignant progression of GBM; promotes proliferation, invasion and migration of DGCs.
Molecular mechanism: Exosomal circCMTM3 binds CNOT4 to block E3-ligase-mediated ubiquitination degradation of STAT5A/STAT5B; acts as a molecular scaffold to rearrange JAK2-STAT5A/STAT5B interactions, increasing STAT5A phosphorylation and nuclear translocation; STAT5A transcriptionally upregulates CHI3L2 and SRSF1, forming a circCMTM3/STAT5A/SRSF1 positive feedback loop.
Biological pathway or process:

JAK/STAT (promotes); angiogenesis (promotes); migration (promotes); invasion (promotes); proliferation (promotes); ceRNA regulation (other); other pathway/process (promotes)
Detected method:
Q
S
Validation methods:

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

High exosomal circCMTM3 correlates with higher glioma grade and shorter overall survival (poor prognosis).
Description:

Exosomal circCMTM3 is up-regulated in glioblastoma and is associated with higher glioma grade and poor prognosis. It promotes proliferation, invasion/migration, and vasculogenic mimicry in differentiated glioma cells by binding CNOT4 to inhibit STAT5A/STAT5B ubiquitination-degradation and by scaffolding JAK2-STAT5 signaling to enhance STAT5A phosphorylation, inducing CHI3L2 and SRSF1 and sustaining a circCMTM3/STAT5A/SRSF1 positive feedback loop.
Confidence score:

0.8969
Other information
Title:

Dual role of exosomal circCMTM3 derived from GSCs in impeding degradation and promoting phosphorylation of STAT5A to facilitate vasculogenic mimicry formation in glioblastoma.

Journal: Theranostics
Published: 2024
PubMed ID: 39310105
Study type:

combined biological and clinical study
Data availability: TCGA; CGGA693; CGGA325
Code availability: -