circRNA basic information
circBase ID: hsa_circ_0065394
Name: hsa_circ_PFKFB4
Synonym: -
Host Gene: PFKFB4
Genomic location(hg19): chr3:48581012-48587667:-
Genomic location(hg38): chr3:48543579-48550234:-
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

Cell lines:

HPDE6-C7; AsPC-1; BxPC-3; Capan-1; PANC-1; PL45

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: hnRNP L, hnRNP G, hnRNP A1, PKM, PKM2
Associated microRNA: -
Biological function: Promotes proliferation, migration, invasion, glycolysis, tumor growth and metastasis of pancreatic cancer cells under hypoxia.
Molecular mechanism: hsa_circ_0065394 is generated via hnRNP L and Alu repeats, localizes to nucleus and cytoplasm, and encodes a 94-aa protein (cPFKFB4) via an IRES-dependent cap-independent translation mechanism; cPFKFB4 binds hnRNP G to disrupt hnRNP G-hnRNP A1 interaction, enhances hnRNP A1-mediated PKM alternative splicing, increases PKM2, and strengthens glycolysis under hypoxia.
Biological pathway or process:

glycolysis (promotes); proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); oxidative phosphorylation (inhibits)

Detected method:
Q
H
Validation methods:

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

Clinical significance:

Up-regulated in PC tissues, associated with tumor size, shows diagnostic potential (ROC AUC 0.677), and high expression is associated with worse overall survival.

Description:

hsa_circ_0065394 is up-regulated in pancreatic cancer, especially under hypoxia, and promotes tumor cell proliferation, migration/invasion and in vivo growth. It encodes an IRES-driven protein cPFKFB4 that binds hnRNP G, disrupts hnRNP G-hnRNP A1 interaction, enhances PKM alternative splicing toward PKM2, and increases glycolysis.

Confidence score:

0.8999

Other information
Title:

A novel protein cPFKFB4 encoded by hsa_circ_0065394 strengthens PKM2-mediated glucose metabolic reprogramming to facilitate pancreatic cancer progression under hypoxia.

Journal: Molecular cancer
Published: 2025
PubMed ID: 41219790
Study type:

combined biological and clinical study

Data availability: -
Code availability: -