circRNA basic information
circBase ID: -
Name: hsa_circ_METTL3
Synonym: circMETTL3 / cirMETTL3
Host Gene: METTL3
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0015542
MONDO name: secondary hemophagocytic lymphohistiocytosis
Disease details: Secondary Hemophagocytic lymphohistiocytosis / sHLH
Disease DO ID:
 -
Disease MeSH ID:
 -
Disease NCIt ID:
 C121184
Disease ICD11 ID:
 -
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

plasma; plasma exosomes; peripheral blood; PBMC; CD11b+ monocytes
Cell lines:

THP1; THP-1; 293 T; HEK293T
In vivo animal model:

other disease animal model
circRNA-disease information
Expression pattern:
UP
Associated gene: LDHA, SRSF10
Associated microRNA: -
Biological function: promotes M1 macrophage polarization and macrophage activation; induces cytokine storms; enhances glycolysis
Molecular mechanism: circRNA encodes peptide METTL3-156aa; METTL3-156aa binds LDHA to enhance glycolysis and lactate production; lactate induces H3K18la and upregulates SRSF10, which promotes pre-METTL3 splicing to increase circMETTL3 (positive feedback loop)
Biological pathway or process:

glycolysis (promotes); macrophage polarization (promotes); immune regulation (other); inflammation (promotes); other pathway/process (promotes)
Detected method:
Q
M
Validation methods:

Microarray; RT-qPCR; RNase R Treatment; Sanger Sequencing; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; Clinical Sample Validation; ROC Analysis; RIP (RNA Immunoprecipitation); Transfection; Luciferase Reporter Assay; RNA Pull-Down; Co-IP; IF (Immunofluorescence); Flow Cytometry（Non-apoptosis/cycle）; Western Blot; ELISA; ChIP / ChIP-seq; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining; Survival Analysis; Bioinformatics Analysis
Clinical significance:

upregulated in sHLH patient plasma exosomes and evaluated as a diagnostic biomarker (AUC = 0.7977)
Description:

circMETTL3 is up-regulated in plasma exosomes of pediatric sHLH and has diagnostic potential. It promotes M1 macrophage polarization and cytokine storm by encoding METTL3-156aa, which binds LDHA to enhance macrophage glycolysis and lactate production; lactate upregulates SRSF10 via histone lactylation to increase circMETTL3 biogenesis, forming a positive feedback loop.
Confidence score:

0.8905
Other information
Title:

CircMETTL3-156aa reshapes the glycolytic metabolism of macrophages to promote M1 polarization and induce cytokine storms in sHLH.

Journal: Cell death discovery
Published: 2024
PubMed ID: 39384750
Study type:

combined biological and clinical study
Data availability: The online version contains supplementary material available at 10.1038/s41420-024-02202-0; The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request.
Code availability: -