circRNA basic information
circBase ID: -
Name: hsa_circ_DNA2
Synonym: circ16
Host Gene: DNA2
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005575
MONDO name: colorectal cancer
Disease details: colorectal cancer
Disease DO ID:
5672, 9256
Disease MeSH ID:
-
Disease NCIt ID:
C4978
Disease ICD11 ID:
-
Disease OMIM ID:
114500
Species: Human
Species details: Homo sapiens
Tissue specimen:

CRC tissues; adjacent normal tissues; colon cancer tissue microarrays; tumor tissues

Cell lines:

HCT116; SW480; RKO; SW620; FHC; CCC-HIE-2; HeLa; A549; MCF7; HepG2; HEK293T; 293FT

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: IGF2BP3, c-Myc mRNA, c-Myc, CXCL10, IL-9, IFN-g, JAK1, JAK2, STAT1, CD8 + T cells
Associated microRNA: -
Biological function: circDNA2v maintains the oncogenic phenotype of CRC cells, prevents cellular senescence and cell-cycle arrest, promotes proliferation and clonogenicity, and its silencing induces a proinflammatory SASP that recruits and activates CD8 + T cells.
Molecular mechanism: circDNA2v directly binds IGF2BP3, prevents IGF2BP3 ubiquitination and proteasomal degradation, facilitates IGF2BP3 binding to c-Myc mRNA, and stabilizes c-Myc mRNA. circDNA2v silencing activates IFN-g/JAK-STAT1 signaling to enhance CXCL10 and IL-9 secretion.
Biological pathway or process:

proliferation (promotes); cell cycle (promotes); mRNA stability (promotes); ubiquitination (inhibits); JAK/STAT (inhibits); immune regulation (inhibits); other pathway/process (inhibits)

Detected method:
Q
B
S
Validation methods:

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

Clinical significance:

High circDNA2v expression in CRC tumors is associated with significantly shorter overall survival and lower intratumoral CD8 + T cell infiltration.

Description:

circDNA2v is a DNA2-derived human circRNA upregulated in colorectal cancer and associated with poor overall survival. Mechanistically, it binds IGF2BP3, protects IGF2BP3 from ubiquitin-mediated degradation, and stabilizes c-Myc mRNA to maintain CRC cell proliferation and prevent senescence. Silencing circDNA2v induces senescence and a JAK-STAT1-dependent SASP enriched for CXCL10 and IL-9, promoting CD8 + T cell recruitment and cytotoxicity.

Confidence score:

0.8898

Other information
Title:

Targeting high circDNA2v levels in colorectal cancer induces cellular senescence and elicits an anti-tumor secretome.

Journal: Cell reports
Published: 2024
PubMed ID: 38615319
Study type:

combined biological and clinical study

Data availability: GEO: GSE211804; iProX: IPX0005402000
Code availability: -