circRNA basic information
circBase ID: hsa_circ_0000591
Name: hsa_circ_MGA
Synonym: circMGA
Host Gene: MGA
Genomic location(hg19): chr15:41961025-41962156:+
Genomic location(hg38): chr15:41668827-41669958:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0004986
MONDO name: urinary bladder carcinoma
Disease details: bladder cancer / BCa
Disease DO ID:
4007
Disease MeSH ID:
-
Disease NCIt ID:
C4912
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

bladder cancer tissues; paired adjacent normal bladder tissues; tumor tissues

Cell lines:

SV-HUC-1; EJ; T24T; UMUC3

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
DN
Associated gene: HNRNPL, CCL5 mRNA
Associated microRNA: -
Biological function: Acts as a tumor-suppressing circRNA that enhances CCL5 expression and secretion, recruits CD8+ T cells, promotes immune killing of bladder cancer cells, suppresses xenograft tumor growth, and potentiates anti-PD-1 immunotherapy.
Molecular mechanism: circMGA interacts with HNRNPL in the cytoplasm, promotes HNRNPL binding to CCL5 mRNA 3′-UTR, stabilizes CCL5 mRNA, increases CCL5 expression and secretion, and recruits CD8+ T cells; HNRNPL also stabilizes circMGA, forming a positive feedback loop.
Biological pathway or process:

mRNA stability (promotes); immune regulation (promotes); apoptosis (promotes); proliferation (inhibits); drug resistance (other); other pathway/process (promotes)

Detected method:
Q
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; RNA-seq; FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; Flow Cytometry(Non-apoptosis/cycle); Transwell Assay; TUNEL; In Vivo Animal Model; IHC (Immunohistochemistry); ELISA; Western Blot; Cohort Study; Survival Analysis; Bioinformatics Analysis

Clinical significance:

circMGA is downregulated in bladder cancer, negatively associated with pathological stage and grade, and low circMGA expression is associated with poor overall survival; circMGA may be a target for combination immunotherapy with PD-1 checkpoint blockade.

Description:

circMGA is a human MGA-derived circRNA that is downregulated in bladder cancer and whose higher expression is associated with favorable overall survival. It acts as a cytoplasmic tumor suppressor by binding HNRNPL, stabilizing CCL5 mRNA, increasing CCL5 secretion, recruiting CD8+ T cells, and enhancing anti-PD-1 immunotherapy efficacy.

Confidence score:

0.8981

Other information
Title:

Regulation of CD8+ T cells infiltration and immunotherapy by circMGA/HNRNPL complex in bladder cancer.

Journal: Oncogene
Published: 2023
PubMed ID: 36869127
Study type:

combined biological and clinical study

Data availability: GSE182310; Supplementary Materials; https://doi.org/10.1038/s41388-023-02637-2
Code availability: -