circRNA basic information
circBase ID: mmu_circ_0001052
Name: mmu_circ_HIPK3
Synonym: circHIPK3 / circular HIPK3
Host Gene: HIPK3
Genomic location(hg19): chr11:33307958-33309057:+
Genomic location(hg38): chr11:33286412-33287511:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005015
MONDO name: diabetes mellitus
Disease details: Diabetes mellitus / DM
Disease DO ID:
 9351
Disease MeSH ID:
 D003920
Disease NCIt ID:
 C2985
Disease ICD11 ID:
 465177735
Disease OMIM ID:
 -
Species: Mouse
Species details: Mus musculus
Tissue specimen:

retina; diabetic retinas; fibrovascular membranes; idiopathic epiretinal membranes; peripheral blood; plasma fraction; cellular fraction; aqueous humor
Cell lines:

HRVECs; EA.hy.926; human coronary artery endothelial cells; human umbilical vein endothelial cells; HEK293T cells; human retinal endothelial cells; mouse retinal endothelial cells
In vivo animal model:

other disease animal model
circRNA-disease information
Expression pattern:
UP
Associated gene: Ago2, vascular endothelial growth factor-C, VEGFC, FZD4, WNT2, c-myb
Associated microRNA: miR-30a-3p, miR-30d-3p, miR-30e-3p
Biological function: circHIPK3 promotes retinal endothelial cell viability, proliferation, migration, and tube formation, and contributes to diabetes mellitus-induced retinal vascular dysfunction, vascular leakage, inflammation, and acellular capillary formation.
Molecular mechanism: circHIPK3 functions as a cytoplasmic miRNA sponge for miR-30a-3p, miR-30d-3p, and miR-30e-3p, especially miR-30a-3p, thereby relieving miR-30a-3p-mediated repression and increasing VEGFC, FZD4, and WNT2 expression; c-myb acts as an upstream transcriptional regulator of circHIPK3 under high-glucose and oxidative stress conditions.
Biological pathway or process:

ceRNA regulation (promotes); proliferation (promotes); migration (promotes); angiogenesis (promotes); inflammation (promotes); VEGF/VEGFR (promotes); other pathway/process (promotes)
Detected method:
Q
B
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; Northern Blot; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; MTT; EdU Staining; Transwell Assay; Tube Formation Assay; In Vivo Animal Model; ELISA; ChIP / ChIP-seq; Bioinformatics Analysis
Clinical significance:

circHIPK3 is upregulated in fibrovascular membranes, plasma, and aqueous humor of diabetic patients and is suggested as a potential target to control diabetic proliferative retinopathy and diabetes mellitus-induced vascular complications.
Description:

circHIPK3 is a HIPK3-derived circRNA conserved in human and mouse and is upregulated in diabetic retinas, diabetic patient fibrovascular membranes, plasma, and aqueous humor. It promotes retinal endothelial proliferation, migration, tube formation, vascular leakage, inflammation, and retinal vascular dysfunction by acting as a cytoplasmic sponge for miR-30a-3p and increasing VEGFC, FZD4, and WNT2 expression. Silencing circHIPK3 alleviates diabetes mellitus-induced retinal vascular dysfunction in vivo, suggesting therapeutic relevance.
Confidence score:

0.8626
Other information
Title:

Circular Noncoding RNA HIPK3 Mediates Retinal Vascular Dysfunction in Diabetes Mellitus.

Journal: Circulation
Published: 2017
PubMed ID: 28860123
Study type:

combined biological and clinical study
Data availability: -
Code availability: -