circRNA basic information
circBase ID: hsa_circ_0008035
Name: hsa_circ_EXT1
Synonym: -
Host Gene: EXT1
Genomic location(hg19): chr8:118830673-118849440:-
Genomic location(hg38): chr8:117818434-117837201:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0001056
MONDO name: gastric cancer
Disease details: gastric cancer / GC
Disease DO ID:
10534
Disease MeSH ID:
-
Disease NCIt ID:
C9331
Disease ICD11 ID:
1397617262
Disease OMIM ID:
613659
Species: Human
Species details: Homo sapiens
Tissue specimen:

serum; gastric cancer tissue; normal tissues; paraffin-embedded tissue

Cell lines:

GES-1; SGC7901; MKN-45; AGS; BGC-823; MGC803; HEK293T; YTN16

In vivo animal model:

syngeneic model

circRNA-disease information
Expression pattern:
UP
Associated gene: EXT1-219aa, EXT1, PKM2, CD8+ T cells
Associated microRNA: -
Biological function: promotes gastric cancer progression, proliferation, metabolic reprogramming (glycolysis/pyruvate metabolism), and immune evasion; reduces CD8+ T cell number and function; decreases sensitivity to anti-PD-L1 therapy
Molecular mechanism: encodes EXT1-219aa that suppresses EXT1 phosphorylation/expression, leading to EXT1-dependent regulation of PKM2 glycosylation and nuclear localization; promotes glycolysis/pyruvate metabolism and immune escape via the EXT1/PKM2 axis
Biological pathway or process:

immune regulation (inhibits); glycolysis (promotes); other pathway/process (promotes)

Detected method:
Q
S
Validation methods:

Bioinformatics Analysis; RT-qPCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Transfection; Western Blot; In Vivo Animal Model; Flow Cytometry(Non-apoptosis/cycle); RNA-seq

Clinical significance:

Elevated serum hsa_circ_0008035 correlates with advanced tumor stages and lymph node metastasis; potential diagnostic biomarker/prognostic indicator

Description:

hsa_circ_0008035 is up-regulated in gastric cancer patient serum and cell lines and is associated with advanced stage and lymph node metastasis. It promotes tumor growth and immune evasion by encoding EXT1-219aa to suppress EXT1, thereby enhancing PKM2 nuclear translocation/activity and glycolysis through an EXT1/PKM2 axis, reducing CD8+ T-cell infiltration/function and anti-PD-L1 sensitivity.

Confidence score:

0.6745

Other information
Title:

Hsa_Circ_0008035 drives immune evasion of gastric cancer via promoting EXT1-mediated nuclear translocation of PKM2.

Journal: Translational oncology
Published: 2024
PubMed ID: 39053344
Study type:

combined biological and clinical study

Data availability: GSE78092; GSE147698
Code availability: -