circRNA basic information
circBase ID: hsa_circ_0035435
Name: hsa_circ_CGNL1
Synonym: circ_0035435 / circCGNL1
Host Gene: CGNL1
Genomic location(hg19): chr15:57743697-57754090:+
Genomic location(hg38): chr15:57451499-57461892:+
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0009831
MONDO name: malignant pancreatic neoplasm
Disease details: pancreatic cancer / PC
Disease DO ID:
1793
Disease MeSH ID:
-
Disease NCIt ID:
C9005
Disease ICD11 ID:
542147910
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

PC tissues; adjacent tissues; normal pancreas tissues

Cell lines:

MIA PaCa-2; PANC-1; Capan-1; BxPC-3; HPDE6-C7; HPNE; 293 T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: NUDT4, HDAC4, RUNX2, GAMT, Ago2
Associated microRNA: -
Biological function: inhibits proliferation; promotes apoptosis; suppresses tumor growth
Molecular mechanism: circCGNL1 binds NUDT4 to enhance NUDT4-dependent HDAC4 dephosphorylation and nuclear translocation; nuclear HDAC4 deacetylates RUNX2 promoting RUNX2 degradation; reduced RUNX2 relieves transcriptional inhibition of GAMT; increased GAMT induces apoptosis via AMPK-AKT-Bad signaling
Biological pathway or process:

apoptosis (promotes); proliferation (inhibits); AMPK (promotes); PI3K/AKT (inhibits); other pathway/process (other)

Detected method:
Q
Validation methods:

RT-qPCR; Sanger Sequencing; divergent primers PCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA Pull-Down; Co-IP; GST-Pulldown; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; TUNEL; Annexin V/PI Flow Cytometry; In Vivo Animal Model; IHC (Immunohistochemistry); Western Blot; IF (Immunofluorescence); ChIP / ChIP-seq; Bioinformatics Analysis; Survival Analysis

Clinical significance:

patients with lower circCGNL1 expression had a poorer OS than patients with higher circCGNL1 expression; circCGNL1 was an independent prognostic factor for PC patients

Description:

circCGNL1 is down-regulated in pancreatic cancer and functions as a tumor suppressor by inhibiting proliferation and promoting apoptosis. Mechanistically, circCGNL1 binds NUDT4 to enhance HDAC4 dephosphorylation and nuclear translocation, leading to RUNX2 deacetylation/degradation, derepression of GAMT, and activation of AMPK-AKT-Bad/caspase-3-associated apoptosis. Low circCGNL1 expression is associated with worse overall survival in PC patients.

Confidence score:

0.8862

Other information
Title:

Role of a novel circRNA-CGNL1 in regulating pancreatic cancer progression via NUDT4-HDAC4-RUNX2-GAMT-mediated apoptosis.

Journal: Molecular cancer
Published: 2024
PubMed ID: 38297362
Study type:

combined biological and clinical study

Data availability: 10.1186/s12943-023-01923-7; TCGA; GTEx; UCSC Xena (http://xena.ucsc.edu/)
Code availability: -