circRNA basic information
circBase ID: hsa_circ_0001681
Name: hsa_circ_RAPGEF5
Synonym: circRAPGEF5
Host Gene: RAPGEF5
Genomic location(hg19): chr7:22330793-22357656:-
Genomic location(hg38): chr7:22291174-22318037:-
Subcellular localization: nucleus
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0011962
MONDO name: endometrial cancer
Disease details: endometrial cancer / EC
Disease DO ID:
1380
Disease MeSH ID:
-
Disease NCIt ID:
C27815
Disease ICD11 ID:
-
Disease OMIM ID:
608089
Species: Human
Species details: Homo sapiens
Tissue specimen:

EC tissues; normal endometrial tissues

Cell lines:

KLE; Ishikawa; HEC-1-A; HEC-1-B; RL95-2

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: RBFOX2, TFRC
Associated microRNA: -
Biological function: Promotes EC cell proliferation and tumor growth; confers resistance to ferroptosis (desensitizes cells to erastin/RSL3), decreasing labile iron pool and lipid peroxidation.
Molecular mechanism: Acts as a nuclear decoy binding RBFOX2 (Fox-1 C-terminal domain) to attenuate RBFOX2 binding to TFRC pre-mRNA, promoting TFRC exon-4 skipping (TFRC-S), reducing iron transport, labile iron pool, and lipid peroxide production, thereby causing ferroptosis resistance.
Biological pathway or process:

proliferation (promotes); ferroptosis (inhibits); other pathway/process (other)

Detected method:
Q
S
Validation methods:

RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RNA Pull-Down; RIP (RNA Immunoprecipitation); Transfection; CCK8; EdU Staining; Colony Formation Assay; In Vivo Animal Model; Western Blot; Bioinformatics Analysis; Flow Cytometry(Non-apoptosis/cycle)

Clinical significance:

High circRAPGEF5 expression positively correlates with FIGO stage and histological grade in EC patients.

Description:

circRAPGEF5 is up-regulated in endometrial cancer and mainly nuclear. It binds the splicing factor RBFOX2 and reduces RBFOX2 binding to TFRC pre-mRNA, promoting TFRC exon-4 skipping and lowering labile iron and lipid peroxidation, thereby inhibiting ferroptosis and promoting EC cell proliferation and tumor growth.

Confidence score:

0.8445

Other information
Title:

CircRAPGEF5 interacts with RBFOX2 to confer ferroptosis resistance by modulating alternative splicing of TFRC in endometrial cancer.

Journal: Redox biology
Published: 2022
PubMed ID: 36182807
Study type:

combined biological and clinical study

Data availability: Supplementary data to this article can be found online at https://doi.org/10.1016/j.redox.2022.102493.
Code availability: -