| Expression pattern: |
UP |
| Associated gene: |
MALAT1, IGF2BP3, S100A8, S100A9, FUS, EIF4A3 |
| Associated microRNA: |
- |
| Biological function: |
inhibits M1 macrophage activation; alleviates skin inflammation; inhibits LPS-induced macrophage activation; promotes degradation of S100A8/S100A9 |
| Molecular mechanism: |
hsa_circ_0004287 reduces MALAT1 stability by competitively binding IGF2BP3 with MALAT1 in an m6A-dependent manner, leading to ubiquitination degradation of S100A8/S100A9 and suppression of p38/MAPK phosphorylation and macrophage-mediated inflammation; FUS positively and EIF4A3 negatively regulate hsa_circ_0004287 biogenesis under inflammatory conditions |
| Biological pathway or process: |
MAPK (inhibits); macrophage polarization (inhibits); inflammation (inhibits); m6A modification (other); mRNA stability (inhibits); ubiquitination (promotes); immune regulation (other) |
| Detected method: |
Q
M
|
| Validation methods: |
Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; Microarray; FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); Co-IP; Actinomycin D / DRB Stability Assay; MeRIP / MeRIP-seq; Transfection; ELISA; Western Blot; Flow Cytometry（Non-apoptosis/cycle）; In Vivo Animal Model; H&E Staining; ROC Analysis; Bioinformatics Analysis; RNA-seq |
| Clinical significance: |
hsa_circ_0004287 level in PBMCs could discriminate between AD patients and healthy controls and between psoriasis patients and healthy controls; its expression was negatively correlated with inflammatory cytokines and Scoring Atopic Dermatitis index; it may serve as a therapeutic candidate for AD and psoriasis |
| Description: |
hsa_circ_0004287 is up-regulated in PBMCs of both atopic dermatitis and psoriasis patients and is mainly expressed by macrophages under inflammatory conditions. Functionally, it suppresses M1 macrophage activation and alleviates AD-like and psoriasis-like skin inflammation. Mechanistically, it competitively binds IGF2BP3 to reduce MALAT1 stability in an m6A-dependent manner, promoting S100A8/S100A9 ubiquitination degradation and suppressing p38/MAPK-driven inflammatory activation. |
| Confidence score: |
0.8825 |