circRNA basic information
circBase ID: hsa_circ_0000994
Name: hsa_circ_SLC8A1
Synonym: circSlc8a1
Host Gene: SLC8A1
Genomic location(hg19): chr2:40655612-40657444:-
Genomic location(hg38): chr2:40428472-40430304:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005300
MONDO name: chronic kidney disease
Disease details: chronic kidney disease
Disease DO ID:
784
Disease MeSH ID:
D007676
Disease NCIt ID:
C80078
Disease ICD11 ID:
412389819
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

renal biopsy tissue; kidney tissues; kidney specimens; mouse kidney; mouse heart tissue; mouse liver

Cell lines:

HK-2; HKC-8; BUMPT; mouse primary proximal renal TECs; mouse primary renal tubular epithelial cell (RPTEC)

In vivo animal model:

other disease animal model

circRNA-disease information
Expression pattern:
DN
Associated gene: Annexin A2 (ANXA2)
Associated microRNA: -
Biological function: circSLC8A1 maintains tubular epithelial phenotype and limits tubular partial EMT, tubular dedifferentiation, fibrogenesis, renal fibrosis and ANXA2 protein stabilization; loss of circSLC8A1 promotes partial EMT and fibrosis, while overexpression reduces fibrosis in UUO and UIRI mouse models.
Molecular mechanism: circSLC8A1 directly binds Domain IV of ANXA2 and promotes ANXA2 polyubiquitination and ubiquitin-proteasome-dependent degradation; circSLC8A1 deficiency stabilizes ANXA2 protein, driving tubular partial EMT and fibrosis.
Biological pathway or process:

EMT (inhibits); fibrosis (inhibits); ubiquitination (promotes); other pathway/process (other)

Detected method:
Q
H
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; FISH / smFISH; ISH (In Situ Hybridization); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Transfection; CCK8; EdU Staining; Cell Cycle Assay; Western Blot; IHC (Immunohistochemistry); IF (Immunofluorescence); In Vivo Animal Model; H&E Staining; Bioinformatics Analysis; Cohort Study

Clinical significance:

circSLC8A1 is deficient in CKD and lower expression is linked to more severe disease, renal fibrosis, worsening kidney function, no resolution of proteinuria over time, and worse clinical prognosis; it may be a diagnostic and prognostic indicator.

Description:

circSLC8A1/circSlc8a1 is a kidney-enriched circRNA downregulated in human CKD, TGF-beta-induced tubular epithelial cells, and UUO/UIRI renal fibrosis mouse models. Its loss promotes tubular partial EMT and fibrogenesis by stabilizing ANXA2 protein, whereas restoration of circSlc8a1 attenuates renal fibrosis in vivo. Clinically, lower circSLC8A1 expression correlates with worse kidney function, fibrosis severity and poor prognosis.

Confidence score:

0.8892

Other information
Title:

The deficiency of circSLC8A1 fosters tubular partial EMT-induced renal fibrosis through upregulating Annexin A2 signaling.

Journal: Journal of advanced research
Published: 2026
PubMed ID: 41967708
Study type:

combined biological and clinical study

Data availability: PRJNA747937; Supplementary Material; https://doi.org/10.1016/j.jare.2026.04.003
Code availability: -