circRNA basic information
circBase ID: hsa_circ_0057104
Name: hsa_circ_PDK1
Synonym: circPDK1 / hsa_circRNA_102854
Host Gene: PDK1
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: 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 tumor tissues; paired normal tissues; serum exosomes; blood

Cell lines:

Aspc-1; Bxpc-3; CFPAC-1; MIA PaCa-2; PANC-1; PATU-8988; 293 T; HPNE

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: AGO2, BPTF, c-myc, HIF1A, BIN1, UBE2O, RNA polymerase II
Associated microRNA: miR-628-3p
Biological function: Promotes pancreatic cancer cell proliferation, migration/metastasis, and glycolysis; promotes tumor growth in vivo.
Molecular mechanism: Hypoxia/HIF1A transcriptionally activates host gene PDK1 leading to increased circPDK1; circPDK1 sponges miR-628-3p to release BPTF and activate c-myc; circPDK1 also acts as a scaffold enhancing UBE2O-BIN1 interaction to promote ubiquitination-mediated degradation of BIN1, further activating c-myc and glycolysis.
Biological pathway or process:

glycolysis (promotes); proliferation (promotes); migration (promotes); metastasis (promotes); ceRNA regulation (promotes); ubiquitination (promotes)

Detected method:
Q
H
S
Validation methods:

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

Clinical significance:

High circPDK1 expression is associated with advanced pathological stage, lymph node metastasis, and poor prognosis; circPDK1 is abundant in serum exosomes of PC patients but almost absent in healthy controls, suggesting biomarker potential for diagnosis and prognosis.

Description:

circPDK1 is upregulated in pancreatic cancer tissues and serum exosomes and correlates with poor prognosis. Under hypoxia, HIF1A increases circPDK1 via activating the PDK1 promoter. circPDK1 promotes proliferation, migration/metastasis and glycolysis by activating c-myc through a miR-628-3p/BPTF ceRNA axis and by scaffolding UBE2O-mediated ubiquitination/degradation of BIN1.

Confidence score:

0.8995

Other information
Title:

Hypoxia-induced exosomal circPDK1 promotes pancreatic cancer glycolysis via c-myc activation by modulating miR-628-3p/BPTF axis and degrading BIN1.

Journal: Journal of hematology & oncology
Published: 2022
PubMed ID: 36068586
Study type:

combined biological and clinical study

Data availability: The datasets supporting the conclusions of this article are included within the article and its additional files.
Code availability: -