circRNA basic information
circBase ID: hsa_circ_0005035
Name: hsa_circ_IGF1R
Synonym: circular RNA IGF1R
Host Gene: IGF1R
Genomic location(hg19): chr15:99250790-99251336:+
Genomic location(hg38): chr15:98707561-98708107:+
Subcellular localization: nucleus and 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:

tumour tissues; human tissues; mouse lungs; lung tissue
Cell lines:

H1975; PC9; HEK-293T; 293 T; Luc-H1975
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: RNA helicase A (RHA), DHX9, IGF1R mRNA, IGF1R pre-mRNA, C-IGF1R, VDAC1, Parkin
Associated microRNA: -
Biological function: cIGF1R enhances the efficacy of EGFR-TKIs, suppresses tumour growth and regrowth, inhibits proliferation, promotes apoptosis, inhibits IGF1R signalling, and its encoded peptide C-IGF1R restricts mitophagy in drug-tolerant persister tumour cells.
Molecular mechanism: cIGF1R binds RHA to hinder RHA-dependent IGF1R pre-mRNA splicing and negatively regulate the IGF1R signalling pathway; cIGF1R also encodes C-IGF1R, which interacts with VDAC1, disrupts VDAC1-Parkin interaction, reduces Parkin-mediated VDAC1 ubiquitination, restricts mitophagy, and promotes apoptosis of DTP cells.
Biological pathway or process:

PI3K/AKT (inhibits); ERK (inhibits); proliferation (inhibits); apoptosis (promotes); autophagy (inhibits); mitochondrial function (other); ubiquitination (inhibits); drug resistance (inhibits); other pathway/process (inhibits)
Detected method:
Q
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; RT-qPCR; RNA-seq; FISH / smFISH; IF (Immunofluorescence); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); RNA Pull-Down; Co-IP; Luciferase Reporter Assay; Transfection; Colony Formation Assay; Annexin V/PI Flow Cytometry; Cell Cycle Assay; Flow Cytometry（Non-apoptosis/cycle）; TUNEL; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Western Blot; Bioinformatics Analysis
Clinical significance:

cIGF1R may be used in combination with EGFR-TKIs to improve initial response rates and expand benefits in NSCLC patients with EGFR mutations.
Description:

cIGF1R is a human IGF1R-derived circRNA downregulated in tumour tissues and dysregulated after EGFR-TKI exposure. It enhances EGFR-TKI efficacy by binding RHA to suppress IGF1R mRNA splicing and IGF1R signalling, while its encoded peptide C-IGF1R blocks Parkin-mediated VDAC1 ubiquitination to restrict mitophagy and drive DTP tumour cells toward apoptosis.
Confidence score:

0.8861
Other information
Title:

C-IGF1R encoded by cIGF1R acts as a molecular switch to restrict mitophagy of drug-tolerant persister tumour cells in non-small cell lung cancer.

Journal: Cell death and differentiation
Published: 2023
PubMed ID: 37689814
Study type:

combined biological and clinical study
Data availability: GSE211854; TCGA-LUAD; Supplementary Table 4; Supplementary Table 5; Supplementary Table 6; Supplementary Table 7; Supplementary Table 8; source data
Code availability: -