circRNA basic information
circBase ID: hsa_circ_0001573
Name: hsa_circ_RREB1
Synonym: circRREB1
Host Gene: RREB1
Genomic location(hg19): chr6:7176887-7189555:+
Genomic location(hg38): chr6:7176654-7189322:+
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005184
MONDO name: pancreatic ductal adenocarcinoma
Disease details: pancreatic ductal adenocarcinoma
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 noncancerous tissues; plasma; tissue microarrays; patient-derived organoids; patient-derived xenograft tumors

Cell lines:

PANC-1; BxPC-3; AsPC-1; CFPAC-1; SW1990; MiaPaCa-2; Capan-1

In vivo animal model:

cell line-derived xenograft; patient-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: PGK1, PTEN, YBX1, NUP153, WNT7B, beta-catenin
Associated microRNA: -
Biological function: Promotes PDAC glycolysis, proliferation, migration, invasion, metastasis, tumor growth, metabolic reprogramming, and stemness maintenance; ASO-mediated targeting suppresses PDAC organoid and PDX growth.
Molecular mechanism: CircRREB1 binds PGK1 and impairs PTEN-mediated dephosphorylation of PGK1 at Y324, increasing PGK1 activity and glycolysis; it also binds YBX1 and NUP153, promotes YBX1 nuclear translocation, recruits YBX1 to the WNT7B promoter, activates WNT7B transcription and Wnt/beta-catenin signaling to maintain stemness.
Biological pathway or process:

glycolysis (promotes); Wnt/beta-catenin (promotes); stemness (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); mitochondrial function (inhibits); mRNA stability (other); other pathway/process (promotes)

Detected method:
Q
B
H
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; Northern Blot; FISH / smFISH; IHC (Immunohistochemistry); IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; Western Blot; Cohort Study; Survival Analysis; ROC Analysis; Bioinformatics Analysis

Clinical significance:

High circRREB1 expression is associated with advanced TNM stage, higher SUVmax, lower overall survival, independent risk for unfavorable OS, and diagnostic potential in plasma; combining circRREB1 with CA19-9 improved diagnostic performance.

Description:

CircRREB1 is a human RREB1-derived oncogenic circRNA upregulated in PDAC and associated with advanced disease, higher glucose uptake, diagnostic potential, and poor survival. It promotes glycolysis by binding PGK1 and preventing PTEN-mediated PGK1 Y324 dephosphorylation, and it maintains stemness by binding YBX1/NUP153, facilitating YBX1 nuclear translocation, activating WNT7B transcription, and stimulating Wnt/beta-catenin signaling. Targeting circRREB1 with ASOs suppresses PDAC cell, organoid, xenograft, and PDX growth, supporting its value as a therapeutic target.

Confidence score:

0.9071

Other information
Title:

CircRREB1 Mediates Metabolic Reprogramming and Stemness Maintenance to Facilitate Pancreatic Ductal Adenocarcinoma Progression.

Journal: Cancer research
Published: 2024
PubMed ID: 39288082
Study type:

combined biological and clinical study

Data availability: OEP005444; The National Omics Data Encyclopedia; https://www.biosino.org/NODE/home; TCGA; UCSC Xena; GSE28375; GSE50827; GSE21501
Code availability: -