Thus, instead of formation of p65/IκBα complex and maintaining the negative feedback loop, circIKBKB results in IKKβ-mediated IκBα phosphorylation and promotion of NF-κB pathway which in turn upregulation of many bone-remodeling factors, and thus, induction of osteoclastogenesis and BC bone metastasis [141]. The gene discussed is NFKB1; the disease is breast cancer.