circRNA basic information
circBase ID: -
Name: hsa_circ_FOXO3
Synonym: circ-FOXO3
Host Gene: FOXO3a
Genomic location(hg19): -
Genomic location(hg38): -
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; non-TNBC tissues; blood; plasma
Cell lines:

MCF-10A; MCF-7; T47D; ZR75-1; MDA-MB-231; BT549; BT474; SKBR3; HCC1937; HCC38
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: WHSC1, H3K36me2, Zeb2
Associated microRNA: -
Biological function: Circ-FOXO3 acts as a tumor suppressor in TNBC by inhibiting cell growth, proliferation, invasion, migration, EMT, and metastasis in vitro and in vivo.
Molecular mechanism: Circ-FOXO3 directly interacts with WHSC1, inhibits WHSC1 nuclear localization and activity, reduces WHSC1-mediated H3K36me2 modification at the Zeb2 promoter, and suppresses Zeb2 transcription/expression, thereby inhibiting TNBC progression.
Biological pathway or process:

proliferation (inhibits); migration (inhibits); invasion (inhibits); metastasis (inhibits); EMT (inhibits); cell cycle (inhibits); other pathway/process (inhibits)
Detected method:
Q
H
S
Validation methods:

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

Low circ-FOXO3 expression in TNBC tissues and blood was associated with lymph node metastasis and unfavorable outcomes; circ-FOXO3 may serve as a predictive prognostic biomarker and therapeutic target for TNBC, and blood circ-FOXO3 may serve as a biomarker for TNBC metastasis.
Description:

Circ-FOXO3 is a human FOXO3a-derived circRNA that is downregulated in TNBC tissues, cells, and blood/plasma. It suppresses TNBC proliferation, invasion, EMT, and metastasis by binding WHSC1 and inhibiting the WHSC1-H3K36me2-Zeb2 axis. Clinically, low circ-FOXO3 expression is associated with lymph node metastasis and unfavorable outcome, while higher expression predicts better prognosis.
Confidence score:

0.8973
Other information
Title:

Circ-FOXO3 inhibits triple-negative breast cancer growth and metastasis via regulating WHSC1-H3K36me2-Zeb2 axis.

Journal: Cellular signalling
Published: 2024
PubMed ID: 38341124
Study type:

combined biological and clinical study
Data availability: Attach file step; Supplementary data online at https://doi.org/10.1016/j.cellsig.2024.111079
Code availability: -