circRNA basic information
circBase ID: -
Name: hsa_circ_SEPT9
Synonym: circSEPT9
Host Gene: SEPT9
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: cytoplasm; extracellular vesicle
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005494
MONDO name: triple-negative breast carcinoma
Disease details: triple negative breast cancer
Disease DO ID:
0060081
Disease MeSH ID:
D064726
Disease NCIt ID:
C71732
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

tumor tissues; plasma; plasma-derived EVs

Cell lines:

MDA-MB-231; MDA-MB-231/ADR

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: KIAA1429, LDHA, AGO2
Associated microRNA: miR-515-5p
Biological function: Promotes proliferation, colony formation, migration, invasion, tumor growth, intercellular transfer of DOX resistance, and chemoresistance; suppresses apoptosis and DOX sensitivity.
Molecular mechanism: LDHA Y10 phosphorylation promotes EV-mediated secretion and transfer of circSEPT9; circSEPT9 acts as a ceRNA sponging miR-515-5p to upregulate KIAA1429, increase m6A methylation, and drive DOX resistance.
Biological pathway or process:

proliferation (promotes); migration (promotes); invasion (promotes); apoptosis (inhibits); metastasis (promotes); ceRNA regulation (promotes); m6A modification (promotes); drug resistance (promotes); chemoresistance (promotes); mRNA stability (other)

Detected method:
Q
Validation methods:

RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; IHC (Immunohistochemistry); Western Blot; ROC Analysis; Bioinformatics Analysis

Clinical significance:

EV-circSEPT9 is a stable and quantifiable biomarker with potential utility for predicting DOX resistance in TNBC; ROC AUC = 0.904, sensitivity 69.23%, specificity 96.77%.

Description:

circSEPT9 is upregulated in DOX-resistant TNBC tissues, cells, plasma, and EVs. LDHA Y10 phosphorylation promotes EV-mediated circSEPT9 release and transfer to sensitive TNBC cells, where circSEPT9 sponges miR-515-5p, upregulates KIAA1429, enhances m6A methylation, and promotes proliferation, invasion, tumor growth, and chemoresistance. EV-circSEPT9 also shows diagnostic potential for identifying DOX resistance in TNBC.

Confidence score:

0.8655

Other information
Title:

Y10 phosphorylation of LDHA promotes the release of extracellular vesicle-derived circSEPT9 to enhance the chemoresistance of triple negative breast cancer cells via modulation of the miR-515-5p/KIAA1429 axis.

Journal: Drug resistance updates : reviews and commentaries in antimicrobial and anticancer chemotherapy
Published: 2026
PubMed ID: 41237467
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; Supplementary data associated with this article can be found in the online version at doi:10.1016/j.drup.2025.101324.
Code availability: -