circRNA basic information
circBase ID: hsa_circ_0007518
Name: hsa_circ_NDUFB2
Synonym: circNDUFB2
Host Gene: NDUFB2
Genomic location(hg19): chr7:140402665-140404763:+
Genomic location(hg38): chr7:140702865-140704963:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0005233
MONDO name: non-small cell lung carcinoma
Disease details: non-small cell lung cancer
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:

primary NSCLC tumorous tissues; adjacent nontumorous tissues; subcutaneous tumor tissues; lung tissues

Cell lines:

A549; H1299; HCC827; H1975; H1703; H460; H1650; BEAS-2B; LLC1; 293 T

In vivo animal model:

cell line-derived xenograft; syngeneic model

circRNA-disease information
Expression pattern:
DN
Associated gene: IGF2BP1, IGF2BP2, IGF2BP3, TRIM25, RIG-I, MAVS, METTL3, METTL14, QKI
Associated microRNA: -
Biological function: inhibits NSCLC cell growth, migration, invasion and metastasis; promotes anti-tumor immunity and immune cell infiltration into TME
Molecular mechanism: acts as a scaffold forming a TRIM25/circNDUFB2/IGF2BPs ternary complex to promote ubiquitination and proteasomal degradation of IGF2BPs (enhanced by m6A on circNDUFB2); binds and activates RIG-I to trigger RIG-I-MAVS innate immune signaling
Biological pathway or process:

ubiquitination (promotes); immune regulation (promotes); STING/IFN (promotes); NF-kappaB (promotes); JAK/STAT (promotes); proliferation (inhibits); migration (inhibits); invasion (inhibits); metastasis (inhibits); m6A modification (promotes)

Detected method:
Q
M
Validation methods:

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

Clinical significance:

circNDUFB2 is frequently downregulated in NSCLC and negatively correlates with malignant features (tumor size, lymph node metastasis, stage).

Description:

circNDUFB2 (hsa_circ_0007518), derived from NDUFB2, is down-regulated in NSCLC and acts as a tumor suppressor. It scaffolds TRIM25 with IGF2BP1/2/3 to promote IGF2BP ubiquitination/proteasomal degradation in an m6A-enhanced manner, and it also activates RIG-I-MAVS innate immune signaling to increase cytokines/chemokines and recruit immune cells into the tumor microenvironment, thereby inhibiting NSCLC growth and metastasis.

Confidence score:

0.8641

Other information
Title:

circNDUFB2 inhibits non-small cell lung cancer progression via destabilizing IGF2BPs and activating anti-tumor immunity.

Journal: Nature communications
Published: 2021
PubMed ID: 33436560
Study type:

combined biological and clinical study

Data availability: GSE158695; GSE156607
Code availability: -