circRNA basic information
circBase ID: hsa_circ_0008324
Name: hsa_circ_EZH2
Synonym: circEZH2
Host Gene: EZH2
Genomic location(hg19): chr7:148529725-148544397:-
Genomic location(hg38): chr7:148832633-148847305:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0007254
MONDO name: breast cancer
Disease details: breast cancer / BC
Disease DO ID:
 1612
Disease MeSH ID:
 -
Disease NCIt ID:
 C9335
Disease ICD11 ID:
 1047754165
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

primary BC tissues; hepatic metastatic tissues; adjacent benign liver tissue; BCLM samples
Cell lines:

MDA-MB-231; BT-549; T-47D; MCF-7; SKBR-3; MCF-10A; HEK293T
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: KLF5, FUS, CXCR4
Associated microRNA: miR-217-5p
Biological function: Promotes breast cancer oncogenesis, proliferation/viability, migration/invasion, EMT, and liver metastasis.
Molecular mechanism: circEZH2 sponges miR-217-5p to upregulate KLF5, which transcriptionally activates FUS to enhance circEZH2 back-splicing, and KLF5 transcriptionally upregulates CXCR4 to promote EMT (positive feedback loop).
Biological pathway or process:

EMT (promotes); metastasis (promotes); proliferation (promotes); migration (promotes); invasion (promotes); ceRNA regulation (promotes)
Detected method:
Q
H
M
Validation methods:

Microarray; RT-qPCR; FISH / smFISH; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Bioinformatics Analysis; RNA Pull-Down; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Wound Healing Assay; Western Blot; ChIP / ChIP-seq; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); IF (Immunofluorescence); Survival Analysis
Clinical significance:

Upregulated circEZH2 predicts worse prognosis in breast cancer patients and is a potential biomarker/target.
Description:

circEZH2 (hsa_circ_0008324), derived from EZH2, is upregulated in breast cancer liver metastases and promotes proliferation, invasion, EMT, and liver metastasis. Mechanistically, it sponges miR-217-5p to increase KLF5, which activates FUS (enhancing circEZH2 back-splicing) and CXCR4 transcription, forming a FUS/circEZH2/KLF5/CXCR4 positive feedback loop. High circEZH2 expression is associated with worse prognosis in breast cancer patients.
Confidence score:

0.8973
Other information
Title:

The FUS/circEZH2/KLF5/ feedback loop contributes to CXCR4-induced liver metastasis of breast cancer by enhancing epithelial-mesenchymal transition.

Journal: Molecular cancer
Published: 2022
PubMed ID: 36224562
Study type:

combined biological and clinical study
Data availability: supplementary material available at 10.1186/s12943-022-01653-2
Code availability: -