circRNA basic information
circBase ID: hsa_circ_0000567
Name: hsa_circ_SETD3
Synonym: circ-SETD3
Host Gene: SETD3
Genomic location(hg19): chr14:99924615-99932150:-
Genomic location(hg38): chr14:99458278-99465813:-
Subcellular localization: cytoplasm; exosome
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005575
MONDO name: colorectal cancer
Disease details: colorectal cancer
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:

colon cancer tissue samples; CRC fresh tissues; cancer tissues; adjacent noncancerous tissues; paraffin samples; xenograft tumors; liver metastatic lesions
Cell lines:

RKO; HCT116
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: RASA4, ErbB3, Akt, p-Akt, HIF1A, exosomes
Associated microRNA: miR-4667-5p, miR-4741, miR-1289, miR-1914-3p
Biological function: circSETD3 functions as a tumor suppressor in CRC, inhibiting CRC cell proliferation, migration, tumor growth and metastasis, enhancing cetuximab sensitivity, and promoting cetuximab-induced apoptosis.
Molecular mechanism: circSETD3 acts as a cytoplasmic miRNA sponge for miR-4667-5p, upregulates RASA4, suppresses Ras/Akt signaling and the ErbB3/Akt positive feedback loop; exosomal circSETD3 delivery also disrupts this feedback loop.
Biological pathway or process:

PI3K/AKT (inhibits); proliferation (inhibits); migration (inhibits); metastasis (inhibits); apoptosis (promotes); ceRNA regulation (other); drug resistance (inhibits); chemoresistance (inhibits); EGFR (other); HIF-1 signaling (inhibits)
Detected method:
Q
Validation methods:

RT-qPCR; RNA-seq; FISH / smFISH; Clinical Sample Validation; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Transwell Assay; Wound Healing Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis
Clinical significance:

Low circSETD3 expression correlates with lymphatic metastasis, TNM stage and poor prognosis; high circSETD3 expression is associated with higher overall survival, and circSETD3 was an independent prognostic factor.
Description:

circSETD3 is downregulated in colorectal cancer and acts as a tumor suppressor. It sponges miR-4667-5p to restore RASA4 expression, thereby suppressing the ErbB3/Akt positive feedback loop, inhibiting proliferation, migration, growth and metastasis, and enhancing cetuximab sensitivity. Clinically, low circSETD3 expression is associated with lymphatic metastasis, advanced TNM stage and poor overall survival.
Confidence score:

0.8157
Other information
Title:

CircSETD3 interrupts the bidirectional positive feedback of ErbB3 and Akt by sponging miR-4667-5p to inhibit colorectal cancer progression and cetuximab resistance.

Journal: International journal of biological macromolecules
Published: 2025
PubMed ID: 40541877
Study type:

combined biological and clinical study
Data availability: PRJNA1181276; https://doi.org/10.1016/j.ijbiomac.2025.145352; available from the corresponding author upon reasonable request
Code availability: -