circRNA basic information
circBase ID: hsa_circ_0001449
Name: hsa_circ_ARHGAP10
Synonym: circARHGAP10 / circOE2
Host Gene: ARHGAP10
Genomic location(hg19): chr4:148860975-148876525:+
Genomic location(hg38): chr4:147939824-147955374:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0004986
MONDO name: urinary bladder carcinoma
Disease details: bladder cancer / BCa
Disease DO ID:
4007
Disease MeSH ID:
-
Disease NCIt ID:
C4912
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

benign bladder tissues; malignant bladder tissues; normal bladder tissue; BCa tissue; tumor tissue

Cell lines:

T24; T24-CR; UM-UC-3; UMUC-3-CR; 293 T

In vivo animal model:

cell line-derived xenograft; patient-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: MAT2A, TRIM25, AGO2
Associated microRNA: -
Biological function: Inhibits cisplatin resistance and stemness by destabilizing MAT2A; increases cisplatin sensitivity; suppresses tumorigenicity and metastasis-related phenotypes under cisplatin treatment conditions.
Molecular mechanism: circARHGAP10 acts as an RNA scaffold to enhance TRIM25-MAT2A interaction, promoting K48-linked ubiquitination and ubiquitin-proteasome degradation of MAT2A; not a ceRNA/miRNA sponge.
Biological pathway or process:

ubiquitination (promotes); ceRNA regulation (inhibits); chemoresistance (inhibits); stemness (inhibits); metastasis (inhibits)

Detected method:
Q
S
Validation methods:

circRNA-seq; RNA-seq; RT-qPCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; IF (Immunofluorescence); Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining; Survival Analysis; Clinical Sample Validation; Cohort Study; Bioinformatics Analysis

Clinical significance:

Higher expression of circARHGAP10 was correlated with better prognosis, lower tumor burden with tumor grades, and lower recurrence rate; circARHGAP10 down-regulation associated with cisplatin-based chemotherapy.

Description:

circARHGAP10 is down-regulated in bladder cancer and cisplatin-resistant BCa cells. It binds MAT2A and TRIM25 and functions as an RNA scaffold to enhance TRIM25-dependent (K48-linked) ubiquitination and proteasomal degradation of MAT2A, thereby suppressing methionine metabolism-associated stemness and reducing cisplatin resistance; higher circARHGAP10 predicts better prognosis and lower recurrence.

Confidence score:

0.8961

Other information
Title:

Methionine orchestrates the metabolism vulnerability in cisplatin resistant bladder cancer microenvironment.

Journal: Cell death & disease
Published: 2023
PubMed ID: 37582769
Study type:

combined biological and clinical study

Data availability: All data used and analyzed in this study are available under reasonable request.
Code availability: -