circRNA basic information
circBase ID: hsa_circ_0020007
Name: hsa_circ_ADD3
Synonym: circ-ADD3
Host Gene: ADD3
Genomic location(hg19): chr10:111876016-111886261:+
Genomic location(hg38): chr10:110116258-110126503:+
Subcellular localization: not tested
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0007256
MONDO name: hepatocellular carcinoma
Disease details: hepatocellular carcinoma / HCC
Disease DO ID:
 684, 686
Disease MeSH ID:
 D006528
Disease NCIt ID:
 C3099
Disease ICD11 ID:
 1294035808
Disease OMIM ID:
 114550
Species: Human
Species details: Homo sapiens
Tissue specimen:

HCC tissues; adjacent normal tissues; plasma; lung tissues
Cell lines:

LO2; SNU-423; HepG2; Hep3B; Huh7; SMMC-7721; MHCC-97L
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: EZH2, CDK1, Ubiquitin, H3K27me3, CDX1, FOXC1, HOXA10, CDH1, DAB2IP, LATS2
Associated microRNA: -
Biological function: Inhibits HCC cell migration, invasion and lung metastasis; functions as a metastasis suppressor.
Molecular mechanism: circ-ADD3 directly binds EZH2 and CDK1, enhances CDK1-EZH2 interaction, promotes EZH2 phosphorylation at Thr-345 and Thr-487, increases EZH2 ubiquitination and degradation, reduces H3K27me3 on anti-metastatic gene promoters, and forms a feedback regulatory circuit with EZH2.
Biological pathway or process:

migration (inhibits); invasion (inhibits); metastasis (inhibits); ubiquitination (promotes); other pathway/process (other)
Detected method:
Q
M
Validation methods:

Microarray; RT-qPCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; Clinical Sample Validation; Transfection; Transwell Assay; In Vivo Animal Model; H&E Staining; RNA Pull-Down; RIP (RNA Immunoprecipitation); Western Blot; IHC (Immunohistochemistry); Co-IP; ChIP / ChIP-seq; Survival Analysis; ROC Analysis; Bioinformatics Analysis
Clinical significance:

High circ-ADD3 expression was negatively correlated with vascular invasion, intrahepatic metastasis and distant metastasis; low circ-ADD3 expression was correlated with worse overall and progression-free survival; plasma circ-ADD3 showed diagnostic utility for HCC with AUC 0.8878.
Description:

circ-ADD3 is a down-regulated human circRNA derived from ADD3 exons 4-12 in HCC tissues, cells and plasma. It suppresses HCC migration, invasion and metastasis by binding EZH2 and CDK1, facilitating CDK1-mediated EZH2 phosphorylation, ubiquitination and degradation, thereby reducing H3K27me3-mediated repression of anti-metastatic genes. Clinically, reduced circ-ADD3 is associated with metastatic features and worse survival, while plasma circ-ADD3 has diagnostic potential for HCC.
Confidence score:

0.8807
Other information
Title:

Circular RNA circ-ADD3 inhibits hepatocellular carcinoma metastasis through facilitating EZH2 degradation via CDK1-mediated ubiquitination.

Journal: American journal of cancer research
Published: 2019
PubMed ID: 31497351
Study type:

combined biological and clinical study
Data availability: -
Code availability: -