Transcriptional downregulation of miR-127-3p by CTCF promotes prostate cancer bone metastasis by targeting PSMB5

Prostate cancer (PCa) is one of the most common cancers in males and particularly tends to metastasize to bone. Currently, metastatic bone disease is incurable, and new therapies need to be developed. Our study aims to determine the role of miR-127-3p in PCa metastasis to bone. The results demonstrate that miR-127-3p is markedly reduced in bone metastasis-positive PCa tissues relative to that in bone metastasis-negative PCa tissues. Furthermore, overexpressing miR-127-3p inhibits PCa cell invasion and migration in vitro by targeting the proteasome β-subunit PSMB5. Moreover, CCCTC-binding factor (CTCF) transcriptionally inhibits miR-127-3p by interacting with the miR-127-3p promoter. Collectively, this study uncovers a novel mechanism of the CTCF/miR-127-3p/PSMB5 axis in promoting PCa bone metastasis, indicating that miR-127-3p could function as a promising therapeutic target against bone metastasis.