circRNA basic information
circBase ID: hsa_circ_0001798
Name: hsa_circ_SPIDR
Synonym: circRNA-CREIT
Host Gene: SPIDR
Genomic location(hg19): chr8:48308935-48320523:+
Genomic location(hg38): chr8:47396375-47407961:+
Subcellular localization: cytoplasm; exosome
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005494
MONDO name: triple-negative breast carcinoma
Disease details: triple-negative breast cancer / TNBC
Disease DO ID:
 0060081
Disease MeSH ID:
 D064726
Disease NCIt ID:
 C71732
Disease ICD11 ID:
 -
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

breast cancer tissues; adjacent normal mammary tissues; tumor samples; plasma
Cell lines:

MDA-MB-231; MDA-MB-468; MDA-MB-436; MCF-7; ZR-75-1; SKBR3; HS578T; MCF10A; HEK-293T; MDA-MB-231/DOXR
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
DN
Associated gene: DHX9, PKR, HACE1, eIF2alpha, RACK1, MTK1
Associated microRNA: -
Biological function: Enhances doxorubicin sensitivity; inhibits stress granule assembly; promotes apoptosis; suppresses proliferation, migration, invasion and EMT in TNBC cells.
Molecular mechanism: Acts as a scaffold to facilitate PKR-HACE1 interaction, promoting K48-linked polyubiquitination and proteasomal degradation of PKR; reduces PKR/eIF2alpha signaling to attenuate stress granule formation, releasing RACK1 to bind MTK1 and activate apoptosis signaling.
Biological pathway or process:

chemoresistance (inhibits); apoptosis (promotes); proliferation (inhibits); migration (inhibits); invasion (inhibits); EMT (inhibits); ubiquitination (promotes); other pathway/process (inhibits)
Detected method:
Q
H
S
Validation methods:

RNA-seq; RT-qPCR; ISH (In Situ Hybridization); Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; Survival Analysis; ROC Analysis; RNA Pull-Down; RIP (RNA Immunoprecipitation); Co-IP; Western Blot; Transfection; MTT; Colony Formation Assay; In Vivo Animal Model; IHC (Immunohistochemistry); Bioinformatics Analysis; CCK8
Clinical significance:

High expression of circRNA-CREIT was associated with a favorable prognosis; circRNA-CREIT in plasma could distinguish breast cancer patients from healthy people (ROC AUC 0.72).
Description:

circRNA-CREIT (hsa_circ_0001798, from SPIDR exons 6-7) is down-regulated in breast cancer/TNBC, especially in doxorubicin-resistant settings. It increases doxorubicin sensitivity by acting as a scaffold that enhances HACE1-mediated K48-linked ubiquitination and proteasomal degradation of PKR, thereby suppressing the PKR/eIF2alpha axis, inhibiting stress granule assembly, and enabling RACK1/MTK1-mediated apoptosis. Clinically, higher circRNA-CREIT correlates with favorable prognosis and it is detectable in plasma with diagnostic potential.
Confidence score:

0.8986
Other information
Title:

CircRNA-CREIT inhibits stress granule assembly and overcomes doxorubicin resistance in TNBC by destabilizing PKR.

Journal: Journal of hematology & oncology
Published: 2022
PubMed ID: 36038948
Study type:

combined biological and clinical study
Data availability: Supplementary material available at 10.1186/s13045-022-01345-w.
Code availability: -