circRNA basic information
circBase ID: hsa_circ_0005505
Name: hsa_circ_IRAK3
Synonym: circIRAK3
Host Gene: IRAK3
Genomic location(hg19): chr12:66597490-66622150:+
Genomic location(hg38): chr12:66203710-66228370:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005178
MONDO name: osteoarthritis
Disease details: osteoarthritis
Disease DO ID:
 8398
Disease MeSH ID:
 D010003
Disease NCIt ID:
 C3293
Disease ICD11 ID:
 558562409
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

human OA cartilage; healthy cartilage tissues; plasma; synovium tissues; mouse cartilage; mouse joint
Cell lines:

PHCs; hBMSCs; SW1353; HEK293; HEK-293T
In vivo animal model:

other disease animal model; genetically engineered animal model
circRNA-disease information
Expression pattern:
UP
Associated gene: HNRNP U, IL-1beta mRNA, TNF-alpha mRNA, IL-6 mRNA
Associated microRNA: -
Biological function: circIRAK3 protects chondrocytes by inhibiting apoptosis, promoting proliferation, reducing proinflammatory cytokine expression, delaying cartilage degeneration, and supporting hBMSC chondrogenesis.
Molecular mechanism: circIRAK3 binds HNRNP U and competitively prevents HNRNP U binding to IL-1beta, TNF-alpha, and IL-6 mRNAs, thereby destabilizing these proinflammatory cytokine mRNAs and promoting their degradation.
Biological pathway or process:

inflammation (inhibits); apoptosis (inhibits); proliferation (promotes); mRNA stability (inhibits); other pathway/process (inhibits)
Detected method:
Q
H
S
M
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; Microarray; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; FISH / smFISH; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; EdU Staining; Colony Formation Assay; Annexin V/PI Flow Cytometry; IHC (Immunohistochemistry); IF (Immunofluorescence); ELISA; Western Blot; In Vivo Animal Model; Bioinformatics Analysis
Clinical significance:

circIRAK3 expression in plasma increased with higher OARSI scores and may serve as a diagnostic biomarker, indicator of OA progression, and therapeutic target for OA.
Description:

circIRAK3 is up-regulated in OA cartilage and plasma and acts as a compensatory anti-inflammatory regulator. It binds HNRNP U, reduces HNRNP U-mediated stabilization of IL-1beta, TNF-alpha, and IL-6 mRNAs, and thereby promotes proinflammatory cytokine mRNA degradation. Functionally, circIRAK3 protects chondrocytes, supports hBMSC chondrogenesis, delays DMM-induced cartilage degeneration, and may serve as an OA biomarker and therapeutic target.
Confidence score:

0.8834
Other information
Title:

CircIRAK3 exerts negative feedback regulation on inflammation by binding to HNRNP U and destabilizing proinflammatory cytokine mRNA in osteoarthritis and chondrogenesis.

Journal: International journal of biological macromolecules
Published: 2024
PubMed ID: 38016613
Study type:

combined biological and clinical study
Data availability: The datasets supporting the conclusions of this article are included within the article and its additional files; Supplementary data to this article can be found online at https://doi.org/10.1016/j.ijbiomac.2023.128453
Code availability: -