circRNA basic information
circBase ID: hsa_circ_0000376
Name: -
Synonym: Homo sapiens circular RNA 0000376
Host Gene: -
Genomic location(hg19): chr12:11199618-11248400:-
Genomic location(hg38): chr12:11047019-11095801:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005061
MONDO name: lung adenocarcinoma
Disease details: lung adenocarcinoma
Disease DO ID:
3910
Disease MeSH ID:
C538231
Disease NCIt ID:
C3512
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

LUAD tumors; matching adjacent non-cancerous tissues; xenograft tumors

Cell lines:

16HBE; A549; H1299; H1975

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: IGF2BP3, SLC2A1 mRNA
Associated microRNA: -
Biological function: Accelerates malignant progression, promotes LUAD cell proliferation, migration and invasion, inhibits apoptosis, promotes neutrophil N2 polarization, and supports glucose uptake and lactate production.
Molecular mechanism: hsa_circ_0000376 binds the RNA-binding protein IGF2BP3, strengthens the IGF2BP3-SLC2A1 mRNA interaction, enhances m6A-associated SLC2A1 mRNA stability, and thereby promotes LUAD malignant phenotypes and neutrophil N2 polarization.
Biological pathway or process:

proliferation (promotes); migration (promotes); invasion (promotes); apoptosis (inhibits); immune regulation (promotes); glycolysis (promotes); mRNA stability (promotes); m6A modification (promotes)

Detected method:
Q
S
Validation methods:

RT-qPCR; RNA-seq; Clinical Sample Validation; Bioinformatics Analysis; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Wound Healing Assay; Transwell Assay; Flow Cytometry(Non-apoptosis/cycle); ELISA; RIP (RNA Immunoprecipitation); CLIP; FISH / smFISH; RNA Pull-Down; Actinomycin D / DRB Stability Assay; MeRIP / MeRIP-seq; Western Blot; In Vivo Animal Model; IF (Immunofluorescence); Survival Analysis; ROC Analysis

Clinical significance:

High hsa_circ_0000376 expression is associated with advanced TNM staging, lymph node metastasis, inferior overall survival, and prognostic utility with AUC 0.7917 for forecasting patient mortality.

Description:

hsa_circ_0000376 is upregulated in LUAD tissues and cell lines and high expression is associated with advanced TNM stage, lymph node metastasis, and poor overall survival. Functionally, it promotes LUAD cell proliferation, migration, invasion, tumor growth, glycolytic activity, and neutrophil N2 polarization while suppressing apoptosis. Mechanistically, hsa_circ_0000376 binds IGF2BP3 and stabilizes SLC2A1 mRNA, defining a hsa_circ_0000376/IGF2BP3/SLC2A1 regulatory axis in LUAD.

Confidence score:

0.8611

Other information
Title:

The IGF2BP3/SLC2A1 axis mediates hsa_circ_0000376-Induced malignant progression and neutrophil N2 polarization in the lung adenocarcinoma microenvironment.

Journal: Journal of molecular histology
Published: 2026
PubMed ID: 41729211
Study type:

combined biological and clinical study

Data availability: GSE112214; TCGA-LUAD; circAtlas; ENCORI; RMBase v3.0; Human Protein Atlas; available from the corresponding author on reasonable request
Code availability: -