circRNA basic information
circBase ID: hsa_circ_0000284
Name: hsa_circ_HIPK3
Synonym: circHIPK3
Host Gene: HIPK3
Genomic location(hg19): chr11:33307958-33309057:+
Genomic location(hg38): chr11:33286412-33287511:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005212
MONDO name: rhabdomyosarcoma
Disease details: rhabdomyosarcoma
Disease DO ID:
 3247
Disease MeSH ID:
 D012208
Disease NCIt ID:
 C3359
Disease ICD11 ID:
 -
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

tumor biopsies from primary ERMS; tumor biopsies from primary ARMS; healthy skeletal muscle biopsies
Cell lines:

RH4; RD; U2OS; U2OS DR-GFP; U2OS EJ5-GFP; A172; SKOV-3; A549; MCF7; MCF7 wt/wt; MCF7 wt/del; human primary myoblasts
In vivo animal model:

-
circRNA-disease information
Expression pattern:
UP
Associated gene: BRCA1 mRNA
Associated microRNA: hsa-let7b-5p, hsa-miR21-5p, hsa-miR877-5p
Biological function: circHIPK3 increases BRCA1 translation and supports BRCA1 mRNA stability, thereby regulating DNA-damage response; circHIPK3 depletion decreases BRCA1 protein, increases DNA damage, impairs homologous recombination and non-homologous end joining repair, and sensitizes cancer cells to DNA-damage-inducing agents and PARP inhibition.
Molecular mechanism: circHIPK3 directly pairs with BRCA1 mRNA through its back-splicing junction and competes with FMRP binding to BRCA1 mRNA, alleviating FMRP-mediated repression of BRCA1 translation and possibly mRNA stability.
Biological pathway or process:

mRNA stability (promotes); other pathway/process (promotes); drug resistance (promotes); apoptosis (inhibits)
Detected method:
Q
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; RT-qPCR; RNA-seq; Clinical Sample Validation; RNA Pull-Down; RIP (RNA Immunoprecipitation); CLIP; Luciferase Reporter Assay; Transfection; Flow Cytometry（Non-apoptosis/cycle）; IF (Immunofluorescence); Western Blot; Bioinformatics Analysis
Clinical significance:

Disrupting circHIPK3-BRCA1 mRNA interaction may represent an adjuvant strategy to sensitize BRCA1 wild-type cancer cells to PARP inhibitors, while LNA-mediated competition with FMRP binding may restore BRCA1 levels in BRCA1 hemizygous breast cancer models.
Description:

circHIPK3 is up-regulated in rhabdomyosarcoma cells and patient tumor samples and is studied as a tumor-associated human circRNA across multiple cancer models. It directly binds BRCA1 mRNA through its back-splicing junction, competes with FMRP-mediated translational repression, and thereby supports BRCA1 protein production and DNA-damage response. Depletion or disruption of circHIPK3-BRCA1 interaction lowers BRCA1 levels, increases DNA damage, and sensitizes cancer cells to DNA-damage-inducing agents and PARP inhibition.
Confidence score:

0.8311
Other information
Title:

BRCA1 levels and DNA-damage response are controlled by the competitive binding of circHIPK3 or FMRP to the BRCA1 mRNA.

Journal: Molecular cell
Published: 2024
PubMed ID: 39389065
Study type:

combined biological and clinical study
Data availability: GEO: GSE246226; DOI: https://doi.org/10.17632/fk8bm3rxh2.1; GEO: GSE207453; GEO: GSE39682; TCGA; GENT2; AACR Project GENIE
Code availability: -