circRNA basic information
circBase ID: hsa_circ_0004676
Name: hsa_circ_ADAM22
Synonym: -
Host Gene: ADAM22
Genomic location(hg19): chr7:87593948-87607727:+
Genomic location(hg38): chr7:87964633-87978412:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005494
MONDO name: triple-negative breast carcinoma
Disease details: triple-negative breast cancer
Disease DO ID:
 0060081
Disease MeSH ID:
 D064726
Disease NCIt ID:
 C71732
Disease ICD11 ID:
 -
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

TNBC tissues; adjacent normal tissues; tumor tissues; lung tissues
Cell lines:

MCF-10A; MCF-7; T47D; MDA-MB-468; MDA-MB-231; BT549; HCC1954; HEK293T
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: AGO2, E2F6, PNO1, p53
Associated microRNA: miR-377-3p
Biological function: Promotes TNBC cell proliferation, colony formation, cell cycle progression, migration, invasion, tumorigenesis, angiogenesis-related CD31 expression, and lung metastasis; high expression is associated with poor prognosis.
Molecular mechanism: circ_0004674 acts as a cytoplasmic miRNA sponge for miR-377-3p, thereby upregulating E2F6; E2F6 binds the PNO1 promoter to increase PNO1 expression, and PNO1 promotes p53 ubiquitination and degradation.
Biological pathway or process:

ceRNA regulation (other); proliferation (promotes); cell cycle (promotes); migration (promotes); invasion (promotes); metastasis (promotes); angiogenesis (promotes); p53 signaling (inhibits); ubiquitination (promotes)
Detected method:
Q
B
H
Validation methods:

RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; Northern Blot; FISH / smFISH; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; EdU Staining; Colony Formation Assay; Cell Cycle Assay; Transwell Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis
Clinical significance:

High circ_0004674 expression correlates with tumor volume, lymph node metastasis, distant metastasis, TNM terminal stage, and poor OS and DFS in TNBC patients.
Description:

This study reports that circ_0004674 is up-regulated in TNBC tissues and cell lines and that high expression predicts poor OS and DFS. Functionally, circ_0004674 promotes TNBC proliferation, cell cycle progression, migration, invasion, tumor growth, and metastasis. Mechanistically, it acts as a miR-377-3p sponge to increase E2F6 and downstream PNO1 expression, promoting p53 ubiquitination/degradation and TNBC progression.
Confidence score:

0.8867
Other information
Title:

Circ_0004676 exacerbates triple-negative breast cancer progression through regulation of the miR-377-3p/E2F6/PNO1 axis.

Journal: Cell biology and toxicology
Published: 2023
PubMed ID: 35870038
Study type:

combined biological and clinical study
Data availability: GSE26659; TCGA breast cancer samples; CircInteractome; TargetScan; LinkedOmics; STRING; JASPAR
Code availability: -