circRNA basic information
circBase ID: hsa_circ_0007919
Name: hsa_circ_ABR
Synonym: -
Host Gene: ABR
Genomic location(hg19): chr17:953289-1003975:-
Genomic location(hg38): chr17:1050049-1100735:-
Subcellular localization: nucleus
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005184
MONDO name: pancreatic ductal adenocarcinoma
Disease details: pancreatic ductal adenocarcinoma / PDAC
Disease DO ID:
3498, 3587
Disease MeSH ID:
D021441
Disease NCIt ID:
C9120
Disease ICD11 ID:
581089833
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

PDAC tissues; adjacent tumor tissues

Cell lines:

hTERT-HPNE; PANC-1; CFPAC-1; BxPC-3; MIA-PaCa2; PANC-1/GEM; CFPAC-1/GEM

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: LIG1, FOXA1, TET1, QKI
Associated microRNA: -
Biological function: Promotes gemcitabine resistance, promotes proliferation, inhibits apoptosis, and decreases gemcitabine-induced DNA damage in PDAC cells.
Molecular mechanism: hsa_circ_0007919 binds/recruits FOXA1 and TET1 to the LIG1 promoter, decreases promoter methylation, increases LIG1 transcription, and activates multiple DNA repair pathways; GEM enhances QKI-mediated back-splicing to increase hsa_circ_0007919 biogenesis.
Biological pathway or process:

base excision repair (promotes); mismatch repair (promotes); nucleotide excision repair (promotes); apoptosis (inhibits); proliferation (promotes); drug resistance (promotes)

Detected method:
Q
S
Validation methods:

RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Transfection; CCK8; Annexin V/PI Flow Cytometry; IF (Immunofluorescence); In Vivo Animal Model; IHC (Immunohistochemistry); TUNEL; RIP (RNA Immunoprecipitation); Co-IP; ChIP / ChIP-seq; Luciferase Reporter Assay; MSP (Methylation-Specific PCR); Bioinformatics Analysis

Clinical significance:

High expression of hsa_circ_0007919 predicts poor OS and DFS in PDAC patients (including GEM-resistant/GEM-treated subsets).

Description:

In gemcitabine-resistant PDAC, hsa_circ_0007919 is upregulated and promotes chemoresistance by reducing gemcitabine-induced DNA damage and apoptosis. It localizes mainly in the nucleus and enhances LIG1 transcription by recruiting FOXA1 and TET1 to the LIG1 promoter to reduce promoter methylation, thereby activating multiple DNA repair pathways.

Confidence score:

0.8831

Other information
Title:

hsa_circ_0007919 induces LIG1 transcription by binding to FOXA1/TET1 to enhance the DNA damage response and promote gemcitabine resistance in pancreatic ductal adenocarcinoma.

Journal: Molecular cancer
Published: 2023
PubMed ID: 38044421
Study type:

combined biological and clinical study

Data availability: The data generated in this study are available upon request from the corresponding author.
Code availability: -