circRNA basic information
circBase ID: hsa_circ_0007468
Name: hsa_circ_PRDM4
Synonym: circPRDM4
Host Gene: PRDM4
Genomic location(hg19): chr12:108136973-108140201:-
Genomic location(hg38): chr12:107743196-107746424:-
Subcellular localization: nucleus
 
 
 
 
 
 
 
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:

tumor tissues

Cell lines:

HCCLM3; MHCC97H; Hep3B; HepG2

In vivo animal model:

patient-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: HIF-1alpha, CD274 promoter
Associated microRNA: -
Biological function: promotes immune escape and inhibits CD8+ T cell-mediated anti-tumor immunity under hypoxic conditions by inducing PD-L1 expression
Molecular mechanism: circPRDM4 acts as a scaffold recruiting HIF-1alpha to the CD274 (PD-L1) promoter to enhance HIF-1alpha-mediated transactivation of PD-L1
Biological pathway or process:

immune regulation (inhibits); other pathway/process (promotes)

Detected method:
Q
S
Validation methods:

circRNA-seq; RT-qPCR; RNase R Treatment; divergent primers PCR; Sanger Sequencing; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Western Blot; Flow Cytometry(Non-apoptosis/cycle); ELISA; RNA Pull-Down; RIP (RNA Immunoprecipitation); ChIP / ChIP-seq; Luciferase Reporter Assay; In Vivo Animal Model; H&E Staining; Transfection; Cohort Study; Survival Analysis; Bioinformatics Analysis

Clinical significance:

circPRDM4 was upregulated in responders to PD-1 blockade and associated with therapeutic efficacy; high circPRDM4 expression was associated with prolonged PFS and OS

Description:

In HCC under hypoxia, circPRDM4 promotes immune escape by increasing PD-L1 (CD274) transcription and reducing CD8+ T cell infiltration/cytotoxicity. Mechanistically, it functions in the nucleus as a scaffold that recruits HIF-1alpha to the CD274 promoter to enhance HIF-1alpha-mediated transactivation. Clinically, higher circPRDM4 is enriched in PD-1 blockade responders and associates with longer PFS/OS.

Confidence score:

0.8966

Other information
Title:

Hypoxia-associated circPRDM4 promotes immune escape via HIF-1alpha regulation of PD-L1 in hepatocellular carcinoma.

Journal: Experimental hematology & oncology
Published: 2023
PubMed ID: 36747292
Study type:

combined biological and clinical study

Data availability: available from the corresponding authors on reasonable request
Code availability: -