circRNA basic information
circBase ID: hsa_circ_0071452
Name: hsa_circ_HMGB2
Synonym: circHMGB2
Host Gene: HMGB2
Genomic location(hg19): chr4:174252526-174254146:-
Genomic location(hg38): chr4:173331375-173332995:-
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005233
MONDO name: non-small cell lung carcinoma
Disease details: non-small cell lung cancer / NSCLC
Disease DO ID:
3908
Disease MeSH ID:
D002289
Disease NCIt ID:
C2926
Disease ICD11 ID:
-
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

NSCLC tissues; matched normal tissues; subcutaneous tumors

Cell lines:

A549; PC-9; NCI-H460; NCI-H1299; NCI-H1703; HBE; LLC; HEK-293T

In vivo animal model:

cell line-derived xenograft; syngeneic model; genetically engineered animal model

circRNA-disease information
Expression pattern:
UP
Associated gene: CARM1, HDAC3, STAT1
Associated microRNA: miR-181a-5p
Biological function: promotes NSCLC progression by fostering an immunosuppressive tumor microenvironment, inducing exhaustion of antitumor immunity, and decreasing efficacy of anti-PD-1 therapy; mildly promotes proliferation.
Molecular mechanism: Acts as a ceRNA sponging miR-181a-5p to upregulate CARM1, thereby suppressing type 1 IFN response via HDAC3/STAT1 modulation and promoting immune evasion and anti-PD-1 resistance.
Biological pathway or process:

immune regulation (inhibits); STING/IFN (inhibits); JAK/STAT (inhibits); proliferation (promotes); ceRNA regulation (promotes); drug resistance (promotes)

Detected method:
Q
Validation methods:

RT-qPCR; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; FISH / smFISH; circRIP; RIP (RNA Immunoprecipitation); RNA Pull-Down; Luciferase Reporter Assay; Transfection; CCK8; Colony Formation Assay; Wound Healing Assay; Transwell Assay; Annexin V/PI Flow Cytometry; In Vivo Animal Model; IHC (Immunohistochemistry); Clinical Sample Validation; Survival Analysis; Bioinformatics Analysis; Co-IP; Western Blot; Flow Cytometry(Non-apoptosis/cycle)

Clinical significance:

High circHMGB2 expression indicates poor prognosis in NSCLC and is an independent prognostic factor; higher in patients with progressive disease after anti-PD-1 therapy.

Description:

circHMGB2 (hsa_circ_0071452), derived from HMGB2, is upregulated in NSCLC (including LUAD and LUSC) and predicts poor prognosis. It acts as a ceRNA to sponge miR-181a-5p, increasing CARM1 to suppress the type 1 IFN/JAK-STAT response and promote an immunosuppressive microenvironment, thereby reducing anti-PD-1 therapeutic efficacy.

Confidence score:

0.8879

Other information
Title:

The circular RNA circHMGB2 drives immunosuppression and anti-PD-1 resistance in lung adenocarcinomas and squamous cell carcinomas via the miR-181a-5p/CARM1 axis.

Journal: Molecular cancer
Published: 2022
PubMed ID: 35525959
Study type:

combined biological and clinical study

Data availability: All data in our study are available upon request.
Code availability: -