circRNA basic information
circBase ID: hsa_circ_0058493
Name: hsa_circ_RHBDD1
Synonym: circRHBDD1(4,5)
Host Gene: RHBDD1
Genomic location(hg19): chr2:227729319-227732034:+
Genomic location(hg38): chr2:226864603-226867318:+
Subcellular localization: cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0007254
MONDO name: breast cancer
Disease details: breast cancer bone metastasis
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:

tumor-adjacent normal breast tissues; primary breast cancer tissues; bone metastatic breast cancer tissues (at bone sites); normal breast tissues
Cell lines:

MDA-MB-231; SCP2; 4175; MCF10A; MCF7; T47D; SK-BR-3; ZR75-30; BT549
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: CCL2 mRNA, ELAVL1, RPL22
Associated microRNA: -
Biological function: Promotes osteoclastogenesis, bone-metastatic niche formation, osteolytic bone metastasis, and breast cancer bone metastasis; CMI-blocker disruption of circRHBDD1(4,5)-CCL2 mRNA interaction inhibits osteoclastogenesis and bone metastasis.
Molecular mechanism: circRHBDD1(4,5) directly interacts with the CDS region of CCL2 mRNA and recruits the RNA-binding protein ELAVL1 to enhance CCL2 mRNA stability and translation, thereby increasing CCL2 expression and promoting osteoclastogenesis and breast cancer bone metastasis.
Biological pathway or process:

metastasis (promotes); mRNA stability (promotes); proliferation (promotes); immune regulation (other); other pathway/process (promotes)
Detected method:
Q
H
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; Actinomycin D / DRB Stability Assay; RT-qPCR; ISH (In Situ Hybridization); Nuclear-Cytoplasmic Fractionation; Clinical Sample Validation; RIP (RNA Immunoprecipitation); CLIP; RNA Pull-Down; Transfection; MTT; In Vivo Animal Model; H&E Staining; ELISA; Survival Analysis; Bioinformatics Analysis
Clinical significance:

High circRHBDD1(4,5) expression is positively associated with breast cancer bone metastases and significantly shorter bone-metastasis-free survival.
Description:

circRHBDD1(4,5), also reported as hsa_circ_0058493, is upregulated in bone-tropic metastatic breast cancer cells and bone-metastatic breast cancer tissues. It promotes osteoclastogenesis, bone-metastatic niche formation, and breast cancer bone metastasis by directly binding CCL2 mRNA and recruiting ELAVL1 to enhance CCL2 mRNA stability and translation. High circRHBDD1(4,5) expression is associated with shorter bone-metastasis-free survival, and blocking the circRHBDD1(4,5)-CCL2 mRNA interaction suppresses osteoclastogenesis and bone metastasis in experimental models.
Confidence score:

0.8786
Other information
Title:

CircRHBDD1(4,5)/CCL2 mRNA interaction promotes breast cancer bone metastasis via bone metastatic niche formation.

Journal: Life sciences
Published: 2025
PubMed ID: 40754102
Study type:

combined biological and clinical study
Data availability: manuscript and supplementary information files; Supplementary data to this article can be found online at https://doi. org/10.1016/j.lfs.2025.123885
Code availability: -