circRNA basic information
circBase ID: hsa_circ_0003659
Name: hsa_circ_CDC42BPA
Synonym: circMRCKalpha
Host Gene: -
Genomic location(hg19): chr1:227327276-227335260:-
Genomic location(hg38): chr1:227139575-227147559:-
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0007256
MONDO name: hepatocellular carcinoma
Disease details: hepatocellular carcinoma
Disease DO ID:
684, 686
Disease MeSH ID:
D006528
Disease NCIt ID:
C3099
Disease ICD11 ID:
1294035808
Disease OMIM ID:
114550
Species: Human
Species details: Homo sapiens
Tissue specimen:

tumor tissues; para-tumor tissues; HCC tumors; tumor tissue microarray

Cell lines:

PLC/PRF/5; MHCC97H; HCCLM3; HEK293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: circMRCKalpha-227aa, USP22, HIF-1alpha, CD68 + TAMs, HK2, LDHA, GLUT1/SLC2A1
Associated microRNA: -
Biological function: Promotes HCC glycolysis, proliferation, clonogenesis, migration, invasion, tumor growth, progression, and recurrence risk through encoding circMRCKalpha-227aa.
Molecular mechanism: circMRCKalpha encodes circMRCKalpha-227aa, which binds USP22, increases USP22 protein levels, promotes HIF-1alpha deubiquitination and stabilization, and upregulates glycolytic enzymes.
Biological pathway or process:

glycolysis (promotes); proliferation (promotes); migration (promotes); invasion (promotes); HIF-1 signaling (promotes); ubiquitination (inhibits); metastasis (promotes); other pathway/process (promotes)

Detected method:
Q
H
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; RT-qPCR; FISH / smFISH; ISH (In Situ Hybridization); IHC (Immunohistochemistry); IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Co-IP; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis

Clinical significance:

Elevated circMRCKalpha predicts significantly reduced overall survival, greater cumulative recurrence, and serves as an independent prognostic risk factor in HCC; its expression positively correlates with CD68 + TAM infiltration and USP22 expression.

Description:

circMRCKalpha is a TAM-induced circular RNA upregulated in HCC cells exposed to tumor-associated macrophages. It encodes the peptide circMRCKalpha-227aa, which binds USP22 and stabilizes HIF-1alpha through deubiquitination, promoting glycolysis and HCC progression. Clinically, high circMRCKalpha expression is associated with poor survival and increased recurrence.

Confidence score:

0.8888

Other information
Title:

Tumor-associated macrophage-induced circMRCKalpha encodes a peptide to promote glycolysis and progression in hepatocellular carcinoma.

Journal: Cancer letters
Published: 2024
PubMed ID: 38642609
Study type:

combined biological and clinical study

Data availability: Supplementary data: https://doi.org/10.1016/j.canlet.2024.216872; all data supporting the findings are available upon reasonable request from the corresponding authors
Code availability: -