circRNA basic information
circBase ID: hsa_circ_0004636
Name: hsa_circ_LRBA
Synonym: circLRBA
Host Gene: LRBA
Genomic location(hg19): chr4:151719232-151729550:-
Genomic location(hg38): chr4:150798080-150808398:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0007254
MONDO name: breast cancer
Disease details: breast cancer / BC
Disease DO ID:
 1612
Disease MeSH ID:
 -
Disease NCIt ID:
 C9335
Disease ICD11 ID:
 1047754165
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

BC tissues; paracancerous tissues; adjacent normal breast tissues; normal breast tissues; tumor tissues; human TNBC tissues
Cell lines:

MCF-7; MDA-MB-231; SK-BR-3; BT-549; MCF-10A; 293T; 4T1
In vivo animal model:

cell line-derived xenograft; syngeneic model
circRNA-disease information
Expression pattern:
UP
Associated gene: SPOP, Twist1, PD-L1, Zeb1
Associated microRNA: -
Biological function: Promotes proliferation, invasion, migration, EMT, metastasis, immune evasion, docetaxel resistance and anti-PD-L1 immunotherapy resistance; inhibits CD8+ T cell infiltration; sensitization to DTX upon knockdown.
Molecular mechanism: Zeb1 promotes circLRBA generation; circLRBA directly binds SPOP and competitively disrupts SPOP-Twist1 interaction, suppressing Twist1 ubiquitination and degradation; increased Twist1 enhances PD-L1 promoter binding and transcriptional activation, leading to immune evasion and therapy resistance.
Biological pathway or process:

proliferation (promotes); migration (promotes); invasion (promotes); EMT (promotes); metastasis (promotes); immune regulation (inhibits); chemoresistance (promotes); ceRNA regulation (other)
Detected method:
Q
H
S
Validation methods:

RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; ISH (In Situ Hybridization); Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; Transwell Assay; Wound Healing Assay; ELISA; Western Blot; In Vivo Animal Model; H&E Staining; Survival Analysis; ROC Analysis; Bioinformatics Analysis; IF (Immunofluorescence); IHC (Immunohistochemistry); Cohort Study
Clinical significance:

High circLRBA expression is associated with pathological stage and shorter overall survival; circLRBA is an independent predictor of poor prognosis; ROC AUC 0.678 for BC.
Description:

circLRBA (hsa_circ_0004636), derived from LRBA exons 32-34, is up-regulated in breast cancer and mainly localized in the cytoplasm. It promotes EMT, metastasis, immune evasion and docetaxel/anti-PD-L1 therapy resistance by binding SPOP to block SPOP-mediated Twist1 ubiquitination, thereby stabilizing Twist1 and enhancing PD-L1 transcription; Zeb1 promotes circLRBA generation.
Confidence score:

0.9058
Other information
Title:

CircLRBA Promotes Epithelial-Mesenchymal Transition, Immune Evasion, Chemoimmunotherapy Resistance and Metastasis Through Stabilizing Twist1.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Published: 2025
PubMed ID: 41082269
Study type:

combined biological and clinical study
Data availability: The data that support the findings of this study are available from the corresponding author upon reasonable request.
Code availability: -