circRNA basic information
circBase ID: hsa_circ_0004085
Name: hsa_circ_EPHB2
Synonym: -
Host Gene: EPHB2
Genomic location(hg19): chr1:23107913-23111569:+
Genomic location(hg38): chr1:22781420-22785076:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005575
MONDO name: colorectal cancer
Disease details: colorectal cancer / CRC
Disease DO ID:
5672, 9256
Disease MeSH ID:
-
Disease NCIt ID:
C4978
Disease ICD11 ID:
-
Disease OMIM ID:
114500
Species: Human
Species details: Homo sapiens
Tissue specimen:

tumor tissues; plasma

Cell lines:

LOVO; SW480

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: hnRNP L, hnRNP A1, pre-EPHB2, RRBP1, GRP78 mRNA, ATF6p50, ATF6
Associated microRNA: -
Biological function: promotes oxaliplatin/5-FU chemoresistance by relieving ER stress and inhibiting apoptosis in recipient CRC cells via exosomal transfer
Molecular mechanism: Fn infection promotes hsa_circ_0004085 formation via hnRNP L and exosomal packaging via hnRNP A1; exosomal hsa_circ_0004085 binds RRBP1 to enhance GRP78 mRNA stability and promotes ATF6p50 nuclear translocation, activating UPR components to relieve ER stress and confer chemoresistance
Biological pathway or process:

ERK (not specified); apoptosis (inhibits); ER stress (inhibits); other pathway/process (other)

Detected method:
Q
S
Validation methods:

RNA-seq; RT-qPCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Survival Analysis; Transfection; CCK8; Colony Formation Assay; EdU Staining; Annexin V/PI Flow Cytometry; In Vivo Animal Model; IHC (Immunohistochemistry); IF (Immunofluorescence); H&E Staining; RIP (RNA Immunoprecipitation); RNA Pull-Down; Western Blot; Bioinformatics Analysis

Clinical significance:

High plasma hsa_circ_0004085 before therapy is associated with poor response to oxaliplatin/5-FU and shorter progression-free survival (PFS).

Description:

hsa_circ_0004085 is upregulated in Fn-infected CRC and enriched in tumor-derived exosomes, which transfer it to recipient cells. It binds RRBP1 to stabilize GRP78 mRNA and promotes ATF6p50 nuclear translocation, relieving ER stress, inhibiting apoptosis, and promoting oxaliplatin/5-FU resistance. High plasma levels predict poor chemotherapy response and shorter PFS.

Confidence score:

0.8793

Other information
Title:

Exosomes secreted by Fusobacterium nucleatum-infected colon cancer cells transmit resistance to oxaliplatin and 5-FU by delivering hsa_circ_0004085.

Journal: Journal of nanobiotechnology
Published: 2024
PubMed ID: 38360615
Study type:

combined biological and clinical study

Data availability: The online version contains supplementary material available at 10.1186/s12951-024-02331-9.
Code availability: -