circRNA basic information
circBase ID: hsa_circ_0058495
Name: hsa_circ_RHBDD1
Synonym: circRHBDD1
Host Gene: RHBDD1
Genomic location(hg19): chr2:227729319-227779067:+
Genomic location(hg38): chr2:226864603-226914351:+
Subcellular localization: cytoplasm; exosome
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005184
MONDO name: pancreatic ductal adenocarcinoma
Disease details: pancreatic ductal adenocarcinoma / PDAC
Disease DO ID:
 3498, 3587
Disease MeSH ID:
 D021441
Disease NCIt ID:
 C9120
Disease ICD11 ID:
 581089833
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

PDAC tissues; adjacent non-cancerous tissues; serum; tumor-derived exosomes
Cell lines:

BxPC3; PANC1; SW1990; HPDE6C7; 293T; Pan02; THP-1
In vivo animal model:

genetically engineered animal model; other disease animal model; patient-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: IGF2BP2, TRIM25, MEKK1, EIF4A3
Associated microRNA: -
Biological function: promotes PDAC cell proliferation and invasion; promotes M2 macrophage polarization; fosters an immunosuppressive tumor microenvironment
Molecular mechanism: binds IGF2BP2 to inhibit TRIM25-mediated ubiquitination and attenuate autophagy-lysosome degradation, stabilizing IGF2BP2; stabilized IGF2BP2 (m6A reader) increases MEKK1 mRNA stability to activate ERK1/2 signaling; exosomal transfer promotes M2 macrophage polarization via IGF2BP2-MEKK1 axis
Biological pathway or process:

ERK (promotes); MAPK (promotes); proliferation (promotes); invasion (promotes); macrophage polarization (promotes); immune regulation (promotes); autophagy (inhibits); ubiquitination (inhibits); m6A modification (promotes)
Detected method:
Q
H
S
M
Validation methods:

RNA-seq; Microarray; RT-qPCR; FISH / smFISH; RNase R Treatment; Actinomycin D / DRB Stability Assay; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Western Blot; Transfection; CCK8; EdU Staining; Wound Healing Assay; IHC (Immunohistochemistry); IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Cohort Study; Survival Analysis; In Vivo Animal Model; H&E Staining; ELISA; Flow Cytometry（Non-apoptosis/cycle）; Bioinformatics Analysis
Clinical significance:

High hsa_circ_0058495 expression is significantly associated with shorter OS in PDAC patients and correlates with aggressive pathological features (vascular invasion, perineural invasion, advanced T classification, lymph node metastasis, higher TNM stage).
Description:

hsa_circ_0058495 is upregulated in PDAC tissues, serum, and PDAC-derived exosomes and promotes malignant phenotypes. It binds and stabilizes IGF2BP2 by inhibiting TRIM25-mediated ubiquitination and suppressing autophagy-lysosome degradation, thereby enhancing m6A-dependent MEKK1 mRNA stability and activating ERK1/2 signaling. Exosomal transfer of hsa_circ_0058495 also promotes M2 macrophage polarization to support an immunosuppressive tumor microenvironment and is associated with poor overall survival.
Confidence score:

0.8989
Other information
Title:

Hsa_circ_0058495-mediated IGF2BP2 ubiquitination and m6A modification of MEKK1 promote the progression of PDAC.

Journal: Theranostics
Published: 2025
PubMed ID: 41041073
Study type:

combined biological and clinical study
Data availability: GSE79634; GSE69362
Code availability: -