circRNA basic information
circBase ID: hsa_circ_0039408
Name: hsa_circ_MMP2
Synonym: -
Host Gene: MMP2
Genomic location(hg19): chr16:55522454-55523736:+
Genomic location(hg38): chr16:55488542-55489824:+
Subcellular localization: nucleus and cytoplasm
 
 
 
 
 
 
 
Disease basic information
MONDO ID:
 0007254
MONDO name: breast cancer
Disease details: breast cancer
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; paraffinembedded breast cancer samples; primary breast cancer tissues; bone metastatic breast cancer tissues
Cell lines:

MDA-MB-231; MCF-7; SKBR3; SCP2; 4175
In vivo animal model:

cell line-derived xenograft
circRNA-disease information
Expression pattern:
UP
Associated gene: beta-catenin, PRMT5, S100A4, LGALS3, S100A4 promoters, LGALS3 promoters, WDR5, MLL2
Associated microRNA: -
Biological function: Promotes osteolytic breast cancer bone metastasis by inducing bone metastatic niche formation, disrupting bone homeostasis, promoting osteoclastogenesis, suppressing osteoblastogenesis, and enhancing metastatic capability of breast cancer cells to bone.
Molecular mechanism: circMMP2(6,7) binds S100A4 and LGALS3 promoters and acts as a scaffold to form a circMMP2(6,7)/beta-catenin/PRMT5 complex, recruiting chromatin regulators and inducing PRMT5-dependent histone H3R2me1/H3R2me2s transcriptional activation of S100A4 and LGALS3.
Biological pathway or process:

metastasis (promotes); NF-kappaB (promotes); proliferation (promotes); apoptosis (other); osteoclastogenesis (promotes); osteoblastogenesis (inhibits); other pathway/process (promotes)
Detected method:
Q
H
S
Validation methods:

Back-Splice Junction PCR / divergent primers PCR; RNase R Treatment; Sanger Sequencing; circRNA-seq; Actinomycin D / DRB Stability Assay; RT-qPCR; FISH / smFISH; ISH (In Situ Hybridization); IHC (Immunohistochemistry); Clinical Sample Validation; RNA Pull-Down; ChIP / ChIP-seq; Luciferase Reporter Assay; Transfection; In Vivo Animal Model; H&E Staining; ELISA; Survival Analysis; Bioinformatics Analysis
Clinical significance:

High circMMP2(6,7) expression correlates with breast cancer-bone metastasis and shorter bone metastasis-free survival.
Description:

circMMP2(6,7), also identified as hsa_circ_0039408, is up-regulated in bone metastatic breast cancer and predicts shorter bone metastasis-free survival. It promotes osteolytic bone metastasis by disrupting bone homeostasis through increased osteoclastogenesis and suppressed osteoblastogenesis. Mechanistically, it forms a promoter-associated circMMP2(6,7)/beta-catenin/PRMT5 complex that epigenetically activates S100A4 and LGALS3 transcription, and PRMT5 inhibition with GSK591 blocks this pro-metastatic program.
Confidence score:

0.8908
Other information
Title:

CircMMP2(6,7) Cooperates with beta-Catenin and PRMT5 to Disrupt Bone Homeostasis and Promote Breast Cancer Bone Metastasis.

Journal: Cancer research
Published: 2024
PubMed ID: 37963200
Study type:

combined biological and clinical study
Data availability: PRJNA975116; SRP439238; https://www.ncbi.nlm.nih.gov/sra/ PRJNA975116; supplementary data files
Code availability: -