Epigenetic Activation of CCDC183-AS1 Promotes Osteoclastogenesis and Prostate Cancer Bone Metastasis Through the...

Bone metastasis (BM) is a major contributor to poor prognosis of prostate cancer (PCa); however, the underlying mechanisms of PCa BM remain poorly understood. A better understanding of these processes may provide critical insights for developing effective preventive and therapeutic strategies for PCa BM. In this study, significant upregulation of CCDC183-AS1 in PCa BM is identified, which is associated with disease progression. CCDC183-AS1 overexpression enhanced the ability of PCa cells to spread to the bone by inducing osteoclastogenesis and aiding in the creation of a BM niche. Mechanistically, CCDC183-AS1 interacted with FUBP1 and enhanced its stability by inhibiting JTV-1-mediated ubiquitination and degradation of FUBP1, which promoted the transcription of TNFSF14 (LIGHT). Copy number gain-induced upregulation of KDM5C epigenetically enhanced CCDC183-AS1 expression by recruiting TET1 to its promoter and promoting DNA demethylation. Significantly, the administration of the selective FUBP1 inhibitor, FUBP1-IN-1, is shown to effectively suppress CCDC183-AS1-induced PCa BM. These results shed light on the involvement of CCDC183-AS1 in enhancing osteoclastogenesis and the underlying mechanism in facilitating PCa BM, offering a potential avenue for therapeutic interventions.