circRNA basic information
circBase ID: -
Name: hsa_circ_ZBTB7A
Synonym: circPOK
Host Gene: Zbtb7a
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005089
MONDO name: sarcoma
Disease details: sarcoma
Disease DO ID:
1115
Disease MeSH ID:
D012509
Disease NCIt ID:
C9118
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

human undifferentiated sarcoma primary samples; normal fibrous tissues; osteosarcoma specimens; normal human osteoblasts; mesenchymal tissue; tumors

Cell lines:

HS5; MFH; HT1080

In vivo animal model:

syngeneic model; genetically engineered animal model

circRNA-disease information
Expression pattern:
UP
Associated gene: ILF2, ILF3, Il6 mRNA, Vegf mRNA, Il6 promoter
Associated microRNA: -
Biological function: circPOK acts as a non-coding proto-oncogenic RNA in mesenchymal tumors, promotes tumor formation, tumor cell proliferation, anchorage-independent growth and angiogenesis, and regulates pro-proliferative and pro-angiogenic secreted factors.
Molecular mechanism: circPOK binds the nuclear RNA/DNA-binding proteins ILF2 and ILF3 and functions as a co-activator of the ILF2/3 complex, enhancing ILF2/3-mediated transcriptional regulation and mRNA stabilization of pro-tumorigenic and pro-angiogenic factors such as IL6 and VEGF.
Biological pathway or process:

proliferation (promotes); angiogenesis (promotes); mRNA stability (promotes); other pathway/process (promotes)

Detected method:
Q
S
Validation methods:

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

Clinical significance:

circPOK is increased in human primary undifferentiated sarcoma and osteosarcoma compared with normal counterparts, and targeting circPOK may be beneficial in sarcoma treatment.

Description:

This study identifies circPOK, a Zbtb7a-derived circRNA conserved in mouse and human cells, as an up-regulated proto-oncogenic circRNA in mesenchymal tumors including sarcoma and osteosarcoma. circPOK localizes in both nucleus and cytoplasm and promotes tumor growth, proliferation and angiogenesis by binding ILF2/ILF3 and enhancing ILF2/3-dependent transcriptional and post-transcriptional regulation of pro-proliferative and pro-angiogenic factors such as IL6 and VEGF. Unlike the linear Zbtb7a/Pokemon protein tumor-suppressive axis, circPOK has an independent and antagonistic oncogenic role and may be a therapeutic target in sarcoma.

Confidence score:

0.8817

Other information
Title:

Intragenic antagonistic roles of protein and circRNA in tumorigenesis.

Journal: Cell research
Published: 2019
PubMed ID: 31209250
Study type:

combined biological and clinical study

Data availability: Supplementary Information accompanies this paper at https://doi.org/10.1038/s41422-019-0192-1; Supplementary Information, Table S1; Supplementary Information, Table S2
Code availability: -