circRNA basic information
circBase ID: hsa_circ_0000876
Name: hsa_circ_CHAF1A
Synonym: circRNA-CHAF1A
Host Gene: CHAF1A
Genomic location(hg19): chr19:4405908-4409756:+
Genomic location(hg38): chr19:4405911-4409759:+
Subcellular localization: not tested
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0021042
MONDO name: glioma
Disease details: glioma
Disease DO ID:
 -
Disease MeSH ID:
 D005910
Disease NCIt ID:
 C3059
Disease ICD11 ID:
 -
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

glioma tissues; normal brain tissues; tumor tissues; brain tissue
Cell lines:

GSC19; GSC26; U343; LN229; patient-derived primary glioma stem cells
In vivo animal model:

patient-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: HOXC8, MDM2, p53, p21, FMR1, Ago2
Associated microRNA: miR-211-5p
Biological function: CircCHAF1A promotes proliferation, G1/S phase transition, colony formation, neurosphere/self-renewing capacity, and tumorigenesis of TP53-wildtype glioma stem cells; high circCHAF1A expression is associated with higher WHO grade and shorter survival.
Molecular mechanism: CircCHAF1A acts as a ceRNA/miRNA sponge for miR-211-5p to upregulate HOXC8; HOXC8 transcriptionally upregulates MDM2 and inhibits p53 signaling. FMR1 directly binds circCHAF1A and maintains its stability, while HOXC8 transcriptionally upregulates FMR1, forming an FMR1/circCHAF1A/miR-211-5p/HOXC8 positive feedback loop.
Biological pathway or process:

p53 signaling (inhibits); proliferation (promotes); cell cycle (promotes); ceRNA regulation (promotes); other pathway/process (promotes)
Detected method:
Q
M
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; EdU Staining; Colony Formation Assay; Cell Cycle Assay; IHC (Immunohistochemistry); Western Blot; In Vivo Animal Model; Survival Analysis; Bioinformatics Analysis
Clinical significance:

CircCHAF1A is associated with low survival rate and may serve as a biomarker for diagnosis and prognostic evaluation of glioma and a potential molecular targeted therapy target.
Description:

CircCHAF1A is a CHAF1A-derived human circRNA overexpressed in glioma, especially TP53-wildtype gliomas, and high expression is associated with poorer survival. It promotes TP53wt glioma stem cell proliferation, cell-cycle progression, self-renewal, and intracranial tumorigenesis by sponging miR-211-5p to increase HOXC8, which upregulates MDM2 and suppresses p53 signaling. FMR1 stabilizes circCHAF1A, and HOXC8 transcriptionally induces FMR1, forming a positive FMR1/circCHAF1A/miR-211-5p/HOXC8 feedback loop with biomarker and therapeutic relevance.
Confidence score:

0.88
Other information
Title:

FMR1/circCHAF1A/miR-211-5p/HOXC8 feedback loop regulates proliferation and tumorigenesis via MDM2-dependent p53 signaling in GSCs.

Journal: Oncogene
Published: 2021
PubMed ID: 34017077
Study type:

combined biological and clinical study
Data availability: GSE109569; CGGA; TCGA; supplementary table 1; supplementary table 2; Table S3; Table S4; Table S5; Table S6
Code availability: -