# Epigenetic Activation of CCDC183‐AS1 Promotes Osteoclastogenesis and Prostate Cancer Bone Metastasis Through the FUBP1/LIGHT Axis

## TL;DR

This study identifies a new mechanism by which prostate cancer spreads to the bone, involving a specific gene and potential treatment options.

## Contribution

The study reveals a novel epigenetic mechanism involving CCDC183-AS1 and FUBP1 in promoting prostate cancer bone metastasis.

## Key findings

- CCDC183-AS1 overexpression promotes prostate cancer bone metastasis by inducing osteoclastogenesis.
- CCDC183-AS1 interacts with FUBP1 to enhance its stability and promote LIGHT transcription.
- The FUBP1 inhibitor FUBP1-IN-1 effectively suppresses CCDC183-AS1-induced bone metastasis.

## Abstract

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.

CCDC183‐AS1 overexpression enhanced the ability of PCa cells to spread to the bone by inducing osteoclastogenesis. Mechanistically, CCDC183‐AS1 interacted with FUBP1 and enhanced its stability, which promoted the transcription of TNFSF14 (LIGHT). Copy number gain‐induced KDM5C epigenetically upregulated CCDC183‐AS1 expression by recruiting TET1 to the promoter of CCDC183‐AS1. Significantly, FUBP1‐IN‐1 could effectively suppress CCDC183‐AS1‐induced PCa BM.