circRNA basic information
circBase ID: hsa_circ_0000829
Name: hsa_circ_SPIRE1
Synonym: circSPIRE1
Host Gene: SPIRE1
Genomic location(hg19): chr18:12506475-12535600:-
Genomic location(hg38): chr18:12506476-12535601:-
Subcellular localization: cytoplasm; exosome
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005086
MONDO name: renal cell carcinoma
Disease details: renal cell carcinoma / RCC
Disease DO ID:
4450
Disease MeSH ID:
D002292
Disease NCIt ID:
-
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

RCC tumor tissue; adjacent noncancerous tissues; serum

Cell lines:

786-O; ACHN; 769-P; HK-2; HEK-293T; HUVEC; original PDX; PDX LM

In vivo animal model:

patient-derived xenograft; cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: ELAVL1, GALNT3 mRNA, QKI mRNA, GALNT3, QKI, E-cadherin
Associated microRNA: -
Biological function: suppresses RCC cell migration and metastasis; suppresses mesenchymal state/EMT; suppresses angiogenesis and vascular permeability
Molecular mechanism: Acts as an RBP scaffold/ternary complex: circSPIRE1 binds ELAVL1 and guides ELAVL1 binding to GALNT3 and QKI mRNAs to stabilize them, upregulating GALNT3 and QKI; GALNT3 promotes O-GalNAc glycosylation and membrane localization of E-cadherin; QKI promotes circSPIRE1 biogenesis via flanking introns forming a positive feedback loop; circSPIRE1 is packaged into exosomes and transferred to endothelial cells to suppress permeability and angiogenesis
Biological pathway or process:

migration (inhibits); invasion (inhibits); metastasis (inhibits); EMT (inhibits); angiogenesis (inhibits); ceRNA regulation (inhibits)

Detected method:
Q
B
S
Validation methods:

RNA-seq; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; Northern Blot; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RNA Pull-Down; RIP (RNA Immunoprecipitation); Transfection; Transwell Assay; Wound Healing Assay; Luciferase Reporter Assay; Western Blot; IF (Immunofluorescence); IHC (Immunohistochemistry); Tube Formation Assay; In Vivo Animal Model; H&E Staining; Bioinformatics Analysis; Survival Analysis; ROC Analysis

Clinical significance:

Lower expression correlates with poorer DFS; may predict metastasis; improves DFS predictive ability of SSIGN scoring scale; downregulated in sera of metastatic patients

Description:

circSPIRE1 (hsa_circ_0000829), derived from SPIRE1, is downregulated in metastatic RCC and acts as a metastasis suppressor. It functions mainly as a cytoplasmic/exosomal RNA scaffold: binding ELAVL1 to enhance stabilization of GALNT3 and QKI mRNAs, thereby promoting E-cadherin glycosylation/membrane localization and maintaining an epithelial state; QKI feeds back to promote circSPIRE1 biogenesis. Exosomal circSPIRE1 also suppresses endothelial permeability and angiogenesis, and higher circSPIRE1 associates with better DFS.

Confidence score:

0.8941

Other information
Title:

Exosomal circSPIRE1 mediates glycosylation of E-cadherin to suppress metastasis of renal cell carcinoma.

Journal: Oncogene
Published: 2023
PubMed ID: 37046045
Study type:

combined biological and clinical study

Data availability: Figshare 10.6084/m9.figshare.20293743; TCGA
Code availability: -