circRNA basic information
circBase ID: hsa_circ_0049271
Name: hsa_circ_KEAP1
Synonym: circKEAP1
Host Gene: KEAP1
Genomic location(hg19): chr19:10610070-10610756:-
Genomic location(hg38): chr19:10499394-10500080:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0009807
MONDO name: osteosarcoma
Disease details: Osteosarcoma / OS
Disease DO ID:
3347
Disease MeSH ID:
D012516
Disease NCIt ID:
C9145
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

OS tissues; normal adjacent tissues

Cell lines:

HEK293T; hFOB1.19; U2OS; Saos-2; HOS; MG63

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: vimentin, ARIH1, RIG-I, METTL3, METTL14, FTO, YTHDF1/2
Associated microRNA: -
Biological function: inhibits proliferation; inhibits migration/invasion; inhibits stemness; promotes apoptosis; inhibits metastasis; activates anti-tumor immunity
Molecular mechanism: circKEAP1 encodes KEAP1-259aa; KEAP1-259aa binds vimentin and promotes proteasomal degradation via ARIH1; circKEAP1 binds RIG-I (CARD domain) to activate immune signaling; m6A modification decreases circKEAP1 stability
Biological pathway or process:

proliferation (inhibits); migration (inhibits); invasion (inhibits); metastasis (inhibits); stemness (inhibits); m6A modification (other); STING/IFN (promotes); NF-kappaB (promotes)

Detected method:
Q
M
Validation methods:

Microarray; Bioinformatics Analysis; RT-qPCR; Clinical Sample Validation; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; ISH (In Situ Hybridization); Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Luciferase Reporter Assay; circRNA / peptide; RNA-seq; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Western Blot; MeRIP / MeRIP-seq; ELISA; Survival Analysis; ROC Analysis; IF (Immunofluorescence)

Clinical significance:

circKEAP1 is downregulated in OS tumors and higher circKEAP1 is associated with longer overall survival; ROC AUC 0.76 suggests diagnostic potential

Description:

circKEAP1 (hsa_circ_0049271), derived from KEAP1 exon 2, is down-regulated in osteosarcoma and its higher expression is associated with better overall survival. It suppresses OS proliferation, migration/invasion, stemness and metastasis by encoding KEAP1-259aa, which promotes ARIH1-dependent proteasomal degradation of vimentin, and it also binds RIG-I to activate IFN-related anti-tumor immune signaling; m6A modification decreases circKEAP1 stability.

Confidence score:

0.9012

Other information
Title:

A tumor suppressor protein encoded by circKEAP1 inhibits osteosarcoma cell stemness and metastasis by promoting vimentin proteasome degradation and activating anti-tumor immunity.

Journal: Journal of experimental & clinical cancer research : CR
Published: 2024
PubMed ID: 38383479
Study type:

combined biological and clinical study

Data availability: GSE140256
Code availability: -