| Expression pattern: |
UP |
| Associated gene: |
IKKalpha, IKKbeta, IKKgamma, p65, p50, IkappaBalpha, EIF4A3, M-CSF, GM-CSF |
| Associated microRNA: |
- |
| Biological function: |
Promotes breast cancer bone metastasis by inducing bone pre-metastatic niche formation and promoting osteoclastogenesis. |
| Molecular mechanism: |
Directly binds active IKKbeta and p65 to sustain NF-kappaB activation by promoting IKKbeta-mediated IkappaBalpha phosphorylation and inhibiting the IkappaBalpha negative feedback; recruits NF-kappaB to M-CSF and GM-CSF promoters to increase their expression; circIKBKB cyclization is promoted by EIF4A3 binding to flanking regions. |
| Biological pathway or process: |
NF-kappaB (promotes); osteoclastogenesis (promotes); metastasis (promotes); proliferation (promotes) |
| Detected method: |
Q
H
S
|
| Validation methods: |
circRNA-seq; ISH (In Situ Hybridization); Back-Splice Junction PCR / divergent primers PCR; Sanger Sequencing; RNase R Treatment; Actinomycin D / DRB Stability Assay; RT-qPCR; Clinical Sample Validation; Survival Analysis; Transfection; In Vivo Animal Model; IF (Immunofluorescence); FISH / smFISH; Nuclear-Cytoplasmic Fractionation; RNA Pull-Down; Luciferase Reporter Assay; RIP (RNA Immunoprecipitation); ChIP / ChIP-seq; ELISA; Western Blot; TUNEL; H&E Staining |
| Clinical significance: |
High circIKBKB expression correlates with breast cancer bone metastasis and shorter bone-metastasis-free survival. |
| Description: |
circIKBKB (hsa_circ_0084100, from IKBKB) is up-regulated in bone-metastatic breast cancer and promotes osteolytic bone metastasis. It sustains NF-kappaB signaling by directly interacting with active IKKbeta and p65, disrupting the IkappaBalpha negative feedback loop, and enhances bone remodeling factor (M-CSF/GM-CSF) transcription to drive osteoclastogenesis and pre-metastatic niche formation. High circIKBKB is associated with shorter bone-metastasis-free survival. |
| Confidence score: |
0.8793 |