circRNA basic information
circBase ID: hsa_circ_0000206
Name: hsa_circ_WDR37
Synonym: circWDR37
Host Gene: WDR37
Genomic location(hg19): chr10:1130342-1142186:+
Genomic location(hg38): chr10:1084402-1096246:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
0015459
MONDO name: nasopharyngeal carcinoma
Disease details: nasopharyngeal carcinoma / NPC
Disease DO ID:
9261
Disease MeSH ID:
D00007727; D000077274
Disease NCIt ID:
C3871
Disease ICD11 ID:
1883313543
Disease OMIM ID:
-
Species: Human
Species details: Homo sapiens
Tissue specimen:

NPC tissues

Cell lines:

S18; S26; HONE1; HK1; HEK293T

In vivo animal model:

cell line-derived xenograft

circRNA-disease information
Expression pattern:
UP
Associated gene: PKR, IKKbeta, RELA, IkappaBalpha
Associated microRNA: -
Biological function: Promotes metastasis (migration and invasion) and supports chemotherapy-induced senescence-associated proinflammatory SASP in NPC; circWDR37 deficiency enhances chemotherapy-induced senescence but inhibits metastasis.
Molecular mechanism: circWDR37 binds PKR (dsRBMs domain) and induces PKR homodimerization and phosphorylation, which activates NF-kappaB signaling to induce CCND1 and SASP gene transcription.
Biological pathway or process:

NF-kappaB (promotes); metastasis (promotes); migration (promotes); invasion (promotes); proliferation (promotes); ceRNA regulation (other); other pathway/process (other)

Detected method:
Q
S
M
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; Nuclear-Cytoplasmic Fractionation; FISH / smFISH; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Luciferase Reporter Assay; Transfection; Transwell Assay; Colony Formation Assay; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Western Blot; Clinical Sample Validation; Cohort Study; Survival Analysis; Bioinformatics Analysis; Microarray

Clinical significance:

High circWDR37 expression indicates unfavorable prognosis and is associated with distant metastasis; low circWDR37 levels associate with better response and survival benefit from cisplatin or gemcitabine induction chemotherapy.

Description:

In nasopharyngeal carcinoma, circWDR37 is upregulated in highly metastatic cells and promotes chemotherapy-induced senescence-associated metastasis. It binds PKR in the cytoplasm, induces PKR homodimerization/phosphorylation, activates NF-kappaB, and increases CCND1 and proinflammatory SASP gene transcription, leading to enhanced migration/invasion. Clinically, high circWDR37 associates with poor survival and reduced induction-chemotherapy benefit.

Confidence score:

0.9016

Other information
Title:

Chemotherapy-Induced Senescence Reprogramming Promotes Nasopharyngeal Carcinoma Metastasis by circRNA-Mediated PKR Activation.

Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany)
Published: 2023
PubMed ID: 36683218
Study type:

combined biological and clinical study

Data availability: GSE103611; GSE210410; GSE137543; GSE207871; RDDB2023378121
Code availability: -