circRNA basic information
circBase ID: hsa_circ_0007766
Name: hsa_circ_HER2
Synonym: circ-HER2
Host Gene: HER2
Genomic location(hg19): chr17:37864573-37866734:+
Genomic location(hg38): chr17:39708320-39710481:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0005494
MONDO name: triple-negative breast carcinoma
Disease details: triple negative breast cancer
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:

TNBC cancerous tissues; paired normal tissues / adjacent normal tissues; breast cancer tissues
Cell lines:

MDA-MB-231; MDA-MB-468; BT549; BT474; SK-BR-3; MDA-MB-453; MCF-7; T47D; MCF-10A; HEK293T
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: HER2-103, EGFR, HER3, AKT, Pertuzumab
Associated microRNA: -
Biological function: promotes TNBC cell proliferation, migration/invasion and tumorigenesis; associated with worse overall survival; confers sensitivity to Pertuzumab in circ-HER2/HER2-103-positive TNBC
Molecular mechanism: circ-HER2 is translated to HER2-103; HER2-103 directly binds EGFR/HER3 (CR I domain), promotes EGFR/EGFR homodimerization and EGFR/HER3 heterodimerization, increases EGFR kinase activity and sustains AKT phosphorylation; HER2-103 can be antagonized by Pertuzumab
Biological pathway or process:

PI3K/AKT (promotes); proliferation (promotes); invasion (promotes); migration (promotes); metastasis (promotes); drug resistance (other)
Detected method:
Q
B
S
Validation methods:

circRNA-seq; RNA-seq; Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; Northern Blot; RNase R Treatment; RT-qPCR; FISH / smFISH; Nuclear-Cytoplasmic Fractionation; Actinomycin D / DRB Stability Assay; Transfection; Bioinformatics Analysis; Clinical Sample Validation; Survival Analysis; Western Blot; Luciferase Reporter Assay; RNA Pull-Down; Co-IP; CCK8; Colony Formation Assay; Transwell Assay; In Vivo Animal Model; IHC (Immunohistochemistry); H&E Staining
Clinical significance:

circ-HER2/HER2-103 is expressed in ~30% of TNBC clinical samples and its positivity correlates with worse overall prognosis; identifies a TNBC subset potentially benefiting from Pertuzumab
Description:

In TNBC, circ-HER2 (hsa_circ_0007766) is up-regulated in a subset of patients and is translated into the peptide/protein HER2-103. HER2-103 promotes EGFR/EGFR and EGFR/HER3 dimerization, enhances EGFR kinase activity and sustains AKT phosphorylation, thereby promoting proliferation, invasion/migration and tumorigenesis; circ-HER2 positivity associates with worse overall survival and predicts sensitivity to Pertuzumab in preclinical xenograft models.
Confidence score:

0.8956
Other information
Title:

Circular HER2 RNA positive triple negative breast cancer is sensitive to Pertuzumab.

Journal: Molecular cancer
Published: 2020
PubMed ID: 32917240
Study type:

combined biological and clinical study
Data availability: SRP266211
Code availability: -