circRNA basic information
circBase ID: hsa_circ_0000118
Name: hsa_circ_MAN1A2
Synonym: circMAN1A2
Host Gene: MAN1A2
Genomic location(hg19): chr1:117944807-117963271:+
Genomic location(hg38): chr1:117402185-117420649:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0018177
MONDO name: glioblastoma
Disease details: glioblastoma / GBM
Disease DO ID:
3068
Disease MeSH ID:
D005909
Disease NCIt ID:
C3058
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

GBM tissues; glioma samples; adjacent tissues; paraneoplastic normal tissue

Cell lines:

GSCL1; GSCL3; GSCL4; GSCL7; GSCL8; GSCL9; GSCL7R; GSCL9R; GL261; THP-1

In vivo animal model:

syngeneic model

circRNA-disease information
Expression pattern:
DN
Associated gene: PRPF40B, TEP1, KEAP1, NRF2, ANXA1
Associated microRNA: -
Biological function: Inhibits GSC proliferation, stemness, and invasion; reverses TMZ resistance by inducing ferroptosis; suppresses glioma progression in vivo; reduces TAM recruitment and M2 polarization via NRF2/ANXA1.
Molecular mechanism: circMAN1A2 directly binds TEP1, disrupts TEP1-KEAP1 interaction, promotes KEAP1-mediated NRF2 degradation, inducing ferroptosis; NRF2 transcriptionally upregulates ANXA1 to modulate TAM recruitment and M2 polarization; PRPF40B promotes circMAN1A2 biogenesis.
Biological pathway or process:

ferroptosis (promotes); proliferation (inhibits); invasion (inhibits); stemness (inhibits); chemoresistance (inhibits); immune regulation (inhibits)

Detected method:
Q
S
Validation methods:

circRNA-seq; RNA-seq; Bioinformatics Analysis; RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Western Blot; Transfection; CCK8; EdU Staining; MTT; Flow Cytometry(Non-apoptosis/cycle); In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Survival Analysis; ROC Analysis

Clinical significance:

Lower circMAN1A2 expression is associated with higher WHO grade and poorer prognosis; circMAN1A2 may serve as a biomarker for predicting survival prognosis in glioma patients.

Description:

circMAN1A2 (hsa_circ_0000118) is down-regulated in glioma/GBM and low expression is associated with higher WHO grade and poorer survival. Functionally, circMAN1A2 suppresses GSC malignant phenotypes and increases TMZ sensitivity by inducing ferroptosis. Mechanistically, it binds TEP1 to promote KEAP1-mediated NRF2 degradation, reducing NRF2/ANXA1 signaling linked to TAM recruitment and M2 polarization.

Confidence score:

0.8949

Other information
Title:

CircMAN1A2 Levels Determine GBM Susceptibility to TMZ in a Pathway Involving TEP1- and KEAP1-Mediated NRF2 Degradation Leading to Ferroptosis.

Journal: CNS neuroscience & therapeutics
Published: 2025
PubMed ID: 40583858
Study type:

combined biological and clinical study

Data availability: GSE92322; GSE131928
Code availability: -