circRNA basic information
circBase ID: -
Name: hsa_circ_CDYL
Synonym: Circ-CDYL
Host Gene: CDYL
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: exosome
 
 
 
 
 
 
 
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:

plasma exosomes; HCC tissues; nontumorous adjacent tissues; blood; plasma

Cell lines:

HCCLM3; SMMC-7721

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: HDGF, HIF1AN, METTL3, YTHDC1, hnRNPA2/B1, EpCAM, PI3K P85, PI3K P110, AKT, mTORC1, GSK-3beta, C-MYC, SURVIVIN, pre-CDYL
Associated microRNA: miR-892a, miR-328-3p
Biological function: promotes early hepatocarcinogenesis by enhancing stem-like properties (tumor-initiating capacity), proliferation, spheroid formation and colony formation; promotes malignancy via exosome-mediated intercellular transfer
Molecular mechanism: m6A modification promotes Circ-CDYL biogenesis by enhancing back-splicing via YTHDC1 and promotes exosomal sorting via hnRNPA2/B1; exosomal Circ-CDYL activates HDGF-PI3K-AKT-mTOR and HIF1AN-NOTCH2 signaling in recipient cells; Circ-CDYL acts as a sponge of miR-892a and miR-328-3p to regulate HDGF and HIF1AN
Biological pathway or process:

PI3K/AKT/mTOR (promotes); Notch (promotes); proliferation (promotes); stemness (promotes); ceRNA regulation (promotes)

Detected method:
Q
M
Validation methods:

RT-qPCR; RNase R Treatment; MeRIP / MeRIP-seq; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; In Vivo Animal Model; Flow Cytometry(Non-apoptosis/cycle); Actinomycin D / DRB Stability Assay; Bioinformatics Analysis; ROC Analysis; Clinical Sample Validation; Western Blot; Microarray

Clinical significance:

Plasma exosomal Circ-CDYL (and combined with EpCAM+ exosomes as LTi-Exos, and further combined with AFP) shows high diagnostic accuracy for early HCC (ROC AUC up to 0.90).

Description:

Circ-CDYL is up-regulated in very early/early HCC and is enriched in EpCAM+ plasma exosomes (LTi-Exos). m6A modification (via METTL3) promotes its back-splicing/biogenesis through YTHDC1 and enhances its loading into exosomes through hnRNPA2/B1, enabling exosomal transfer that activates HDGF-PI3K-AKT-mTOR and HIF1AN-NOTCH2 signaling to promote stemness and tumor initiation. Exosomal Circ-CDYL (alone or combined with EpCAM+ exosomes and AFP) shows strong potential for early HCC diagnosis by ROC analysis.

Confidence score:

0.8621

Other information
Title:

N6-methyladenosine modification promotes hepatocarcinogenesis through circ-CDYL-enriched and EpCAM-positive liver tumor-initiating exosomes.

Journal: iScience
Published: 2023
PubMed ID: 37954137
Study type:

combined biological and clinical study

Data availability: https://doi.org/10.1016/j.isci.2023.108022
Code availability: -