circRNA basic information
circBase ID: hsa_circ_0124696
Name: hsa_circ_ROBO1
Synonym: circROBO1
Host Gene: ROBO1
Genomic location(hg19): -
Genomic location(hg38): -
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0007254
MONDO name: breast cancer
Disease details: breast cancer / BC
Disease DO ID:
 1612
Disease MeSH ID:
 -
Disease NCIt ID:
 C9335
Disease ICD11 ID:
 1047754165
Disease OMIM ID:
 -
Species: Human
Species details: Homo sapiens
Tissue specimen:

BC primary tissues; liver metastatic tissues; adjacent normal liver tissues
Cell lines:

BT-549; MDA-MB-231; MDA-MB-468; MCF-7; T-47D; SKBR-3; MCF-10A; 293T; HEK293T
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: KLF5, FUS, BECN1, afadin, NBR1, mTOR, PI3K, AKT
Associated microRNA: miR-217-5p
Biological function: promotes proliferation; promotes migration; promotes invasion; promotes tumor growth; promotes liver metastasis; inhibits selective autophagy of afadin
Molecular mechanism: circROBO1 sponges miR-217-5p to upregulate KLF5; KLF5 transcriptionally activates FUS, which promotes circROBO1 back-splicing (positive feedback loop); circROBO1/KLF5 suppresses BECN1 transcription to inhibit selective autophagy of afadin
Biological pathway or process:

proliferation (promotes); migration (promotes); invasion (promotes); metastasis (promotes); PI3K/AKT (promotes); PI3K/AKT/mTOR (promotes); autophagy (inhibits)
Detected method:
Q
H
S
Validation methods:

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

upregulated expression of circROBO1 was correlated with poor prognosis; BC patients with increased expression of circROBO1 had shorter overall survival; potential prognostic marker and therapeutic target
Description:

circROBO1 is upregulated in breast cancer liver metastases and promotes breast cancer cell proliferation, migration/invasion, tumor growth, and liver metastasis. Mechanistically, circROBO1 sponges miR-217-5p to upregulate KLF5, which transcriptionally activates FUS to enhance circROBO1 back-splicing (positive feedback loop), and circROBO1/KLF5 suppresses BECN1 transcription to inhibit selective autophagy of afadin. High circROBO1 expression is associated with poor overall survival, suggesting prognostic and therapeutic potential.
Confidence score:

0.8878
Other information
Title:

The circROBO1/KLF5/FUS feedback loop regulates the liver metastasis of breast cancer by inhibiting the selective autophagy of afadin.

Journal: Molecular cancer
Published: 2022
PubMed ID: 35073911
Study type:

combined biological and clinical study
Data availability: The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Code availability: -