circRNA basic information
circBase ID: hsa_circ_0000615
Name: hsa_circ_ZNF609
Synonym: CircZNF609
Host Gene: ZNF609
Genomic location(hg19): chr15:64791491-64792365:+
Genomic location(hg38): chr15:64499292-64500166:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0004986
MONDO name: urinary bladder carcinoma
Disease details: bladder cancer
Disease DO ID:
4007
Disease MeSH ID:
-
Disease NCIt ID:
C4912
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

BCa tumours; adjacent tissue samples; peripheral blood; PDX tumours; mouse tumour specimens

Cell lines:

BIU87; T24; RT4; 5637; 253 J; UMUC3; J82; SV-HUC

In vivo animal model:

cell line-derived xenograft; patient-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: IGF2BP2, CD36, DDX39B
Associated microRNA: -
Biological function: CircZNF609 promotes bladder cancer immune escape, inhibits CD8+ T cell anti-tumour activity, suppresses anti-PD-1 immunotherapy sensitivity, promotes tumour growth, and enhances fatty acid uptake by BCa cells.
Molecular mechanism: CircZNF609 binds IGF2BP2 in the cytoplasm, enhances IGF2BP2 interaction with the CD36 3′UTR, increases CD36 mRNA stability in an m6A-dependent manner, promotes CD36-mediated fatty acid uptake, depletes fatty acids in the tumour microenvironment, and induces CD8+ T cell dysfunction; DDX39B regulates circZNF609 nuclear export.
Biological pathway or process:

immune regulation (promotes); lipid metabolism (promotes); mRNA stability (promotes); m6A modification (other); drug resistance (promotes); proliferation (promotes)

Detected method:
Q
Validation methods:

RT-qPCR; RNA-seq; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; IF (Immunofluorescence); RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Actinomycin D / DRB Stability Assay; Transfection; ELISA; Flow Cytometry(Non-apoptosis/cycle); Oil Red O Staining; Western Blot; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Bioinformatics Analysis

Clinical significance:

CircZNF609 holds potential as a biomarker and therapeutic target in bladder cancer immunotherapy and may predict susceptibility to immunotherapy.

Description:

CircZNF609 is an oncogenic circRNA studied in bladder cancer that reduces sensitivity to anti-PD-1 immunotherapy and promotes immune escape. It acts through a circZNF609/IGF2BP2/CD36 mechanism, increasing CD36 mRNA stability and fatty acid uptake by cancer cells, thereby depleting fatty acids in the tumour microenvironment and impairing CD8+ T cell function. The study suggests circZNF609 may serve as a biomarker and therapeutic target for bladder cancer immunotherapy.

Confidence score:

0.8108

Other information
Title:

CircZNF609 inhibited bladder cancer immunotherapy sensitivity via enhancing fatty acid uptake through IGF2BP2/CD36 pathway.

Journal: International immunopharmacology
Published: 2024
PubMed ID: 38878487
Study type:

combined biological and clinical study

Data availability: Data will be made available on request; Supplementary data to this article can be found online at https://doi. org/10.1016/j.intimp.2024.112485
Code availability: -