circRNA basic information
circBase ID: hsa_circ_0001649
Name: hsa_circ_SHPRH
Synonym: circ-SHPRH
Host Gene: SHPRH
Genomic location(hg19): chr6:146209155-146216113:-
Genomic location(hg38): chr6:145888019-145894977:-
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005072
MONDO name: neuroblastoma
Disease details: neuroblastoma
Disease DO ID:
 769
Disease MeSH ID:
 D009447
Disease NCIt ID:
 C3270
Disease ICD11 ID:
 -
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

NB tissues; fresh tumor tissues; NB tumor tissues
Cell lines:

SK-N-BE(2); SH-SY5Y; CHLA-255; 293T
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: SHPRH-146aa, P21, CDKN1A, CDK4, CDK6, Cyclin D, CDK1, GbetaL, Rictor, Sin1
Associated microRNA: -
Biological function: Circ-SHPRH functions as a tumor suppressor in neuroblastoma by inhibiting NB cell proliferation, colony formation, migration, invasion, and in vivo tumor growth, while inducing cell cycle arrest and enhancing the inhibitory effect of everolimus on NB cell proliferation.
Molecular mechanism: Circ-SHPRH encodes the SHPRH-146aa peptide, which upregulates P21, enhances P21 binding to CDK4-Cyclin D complexes, inactivates CDK complexes, induces G1 phase arrest, and suppresses PI3K-Akt-mTOR pathway activity.
Biological pathway or process:

cell cycle (inhibits); proliferation (inhibits); migration (inhibits); invasion (inhibits); PI3K/AKT/mTOR (inhibits); drug resistance (other)
Detected method:
Q
H
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; RT-qPCR; FISH / smFISH; RNA-seq; Clinical Sample Validation; Transfection; Colony Formation Assay; Cell Cycle Assay; Co-IP; MTT; Western Blot; In Vivo Animal Model; H&E Staining; IHC (Immunohistochemistry); Cohort Study; Survival Analysis; Bioinformatics Analysis
Clinical significance:

Decreased circ-SHPRH expression was associated with worse 5-year overall survival, MYCN amplification, advanced INRG stage, and high-risk NB; circ-SHPRH was proposed as a potential biomarker and gene therapeutic agent for NB.
Description:

Circ-SHPRH is downregulated in neuroblastoma and low expression is associated with worse clinical features and poorer survival. Functionally, circ-SHPRH suppresses NB proliferation, migration, invasion, and tumor growth by encoding SHPRH-146aa, which upregulates P21 and inhibits CDK complex activity to induce cell-cycle arrest. The study also suggests circ-SHPRH as a biomarker and potential gene therapy agent, including in combination with the mTOR inhibitor everolimus.
Confidence score:

0.8621
Other information
Title:

Therapeutic SHPRH-146aa encoded by circ-SHPRH dynamically upregulates P21 to inhibit CDKs in neuroblastoma.

Journal: Cancer letters
Published: 2024
PubMed ID: 39002691
Study type:

combined biological and clinical study
Data availability: GSE244294; GSE49710; GSE112734; Supplementary data: https://doi.org/10.1016/j.canlet.2024.217120
Code availability: -