circRNA basic information
circBase ID: hsa_circ_0001947
Name: hsa_circ_AFF2
Synonym: circAFF2
Host Gene: AFF2
Genomic location(hg19): chrX:147743428-147744289:+
Genomic location(hg38): chrX:148661907-148662768:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005575
MONDO name: colorectal cancer
Disease details: colorectal cancer / CRC
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:

pre-treatment colonoscopy specimens; rectal cancer tissues

Cell lines:

HCT-116; HT-29; RKO; SW480; LoVo; SW620; NCM460

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: ALKBH5, YTHDF2, CAND1, Cullin1, NEDD8
Associated microRNA: -
Biological function: enhances radiosensitivity; increases apoptosis after irradiation; inhibits Cullin neddylation
Molecular mechanism: m6A modification-dependent regulation: ALKBH5-mediated demethylation increases circAFF2, while YTHDF2 recognizes m6A-modified circAFF2 and promotes its degradation; circAFF2 binds CAND1 to promote CAND1-Cullin1 interaction and inhibits Cullin1 neddylation
Biological pathway or process:

radioresistance (inhibits); apoptosis (promotes); other pathway/process (inhibits)

Detected method:
Q
H
S
Validation methods:

RNA-seq; MeRIP / MeRIP-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; Transfection; Colony Formation Assay; Annexin V/PI Flow Cytometry; TUNEL; Western Blot; ELISA; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; In Vivo Animal Model; ISH (In Situ Hybridization); IHC (Immunohistochemistry); Clinical Sample Validation; Survival Analysis; Bioinformatics Analysis

Clinical significance:

CircAFF2 was highly expressed in radiosensitive rectal cancer tissues; high circAFF2 expression is associated with higher disease-free survival and can be used as an indicator for screening sensitive populations before chemoradiotherapy.

Description:

In colorectal/rectal cancer, circAFF2 is upregulated in radiosensitive tumors and promotes radiosensitivity by increasing radiation-induced DNA damage responses and apoptosis. It is regulated by m6A dynamics (ALKBH5-mediated demethylation and YTHDF2-dependent decay) and mechanistically binds CAND1 to strengthen CAND1-Cullin1 interaction, thereby inhibiting Cullin neddylation. High circAFF2 expression correlates with better disease-free survival in rectal cancer patients receiving neoadjuvant chemoradiotherapy.

Confidence score:

0.894

Other information
Title:

ALKBH5/YTHDF2-mediated m6A modification of circAFF2 enhances radiosensitivity of colorectal cancer by inhibiting Cullin neddylation.

Journal: Clinical and translational medicine
Published: 2023
PubMed ID: 37381158
Study type:

combined biological and clinical study

Data availability: GSE186940
Code availability: -