circRNA basic information
circBase ID: hsa_circ_0006952
Name: hsa_circ_SMAD4
Synonym: circSMAD4
Host Gene: SMAD4
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005011
MONDO name: Crohn disease
Disease details: Crohn's disease / CD
Disease DO ID:
 8778
Disease MeSH ID:
 D003424
Disease NCIt ID:
 C2965
Disease ICD11 ID:
 1267652425
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

colon tissues; inflamed tissues in the proximal colons; colonic biopsy tissues; isolated epithelial cells; CD4+T cells
Cell lines:

NCM460; HCoEpiC
In vivo animal model:

genetically engineered animal model
circRNA-disease information
Expression pattern:
UP
Associated gene: JAK2, AGO2, STAT3, p-STAT3, occludin, ZO-1
Associated microRNA: miR-135a-5p
Biological function: Promotes experimental colitis and Crohn's colitis progression; impairs intestinal epithelial tight junction proteins and intestinal barrier function; enhances epithelial cell apoptosis; promotes inflammatory cytokine release and imbalance of CD4+ T cell differentiation; si-circSMAD4 ameliorates experimental colitis and protects intestinal barrier function.
Molecular mechanism: circSMAD4 functions as a cytoplasmic ceRNA that sponges miR-135a-5p, thereby upregulating JAK2 and affecting JAK2/STAT3 signaling, tight junction proteins, epithelial apoptosis, intestinal barrier function, inflammation, and CD4+ T cell differentiation.
Biological pathway or process:

ceRNA regulation (promotes); JAK/STAT (promotes); apoptosis (promotes); inflammation (promotes); immune regulation (promotes); other pathway/process (inhibits)
Detected method:
Q
H
M
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; Microarray; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; Annexin V/PI Flow Cytometry; Flow Cytometry（Non-apoptosis/cycle）; TUNEL; In Vivo Animal Model; H&E Staining; ELISA; Western Blot; IF (Immunofluorescence); Bioinformatics Analysis; Cohort Study
Clinical significance:

circSMAD4 expression was associated with endoscopic, biochemical and clinical disease activity of CD and may be a potential therapeutic target.
Description:

circSMAD4 is up-regulated in colon tissues from Crohn's disease patients and in an IL-10 knockout experimental colitis model. It acts mainly in the cytoplasm as a ceRNA that sponges miR-135a-5p to increase JAK2/JAK2-STAT3-related signaling, impair tight junction proteins and barrier integrity, promote epithelial apoptosis and inflammation, and contribute to colitis progression. Inhibition of circSMAD4 by PLGA microsphere-delivered si-circSMAD4 ameliorates experimental colitis and protects intestinal barrier function, suggesting therapeutic potential.
Confidence score:

0.8772
Other information
Title:

circSMAD4 Promotes Experimental Colitis and Impairs Intestinal Barrier Functions by Targeting Janus Kinase 2 Through Sponging miR-135a-5p.

Journal: Journal of Crohn's & colitis
Published: 2023
PubMed ID: 36239525
Study type:

combined biological and clinical study
Data availability: Please contact the corresponding author (Liming Tang) upon reasonable request.
Code availability: -