Previous studies suggested that cell migration inducing hyaluronidase 1 (CEMIP) facilitates hyaluronan catabolism and has a role in cancer metastasis. In this study, we aim to investigate the epigenetic change and possible role of cell migration inducing hyaluronidase 1 (CEMIP) that drives metastatic phenotypes in castration-resistant prostate cancer.

CEMIP was knock-downed (si-RNA) and overexpressed (OE) with lentivirus in androgen-insensitive (DU145, PC-3) and androgen-sensitive (LNCaP) human prostate cancer cell lines. We then performed 3D spheroid model (Aggrewell method) to furtherly confirm that the knock-down and overexpression of CEMIP play crucial role in 3D spheroid formation in castration-resistant prostate cancer cell lines with statistical analysis from GraphPadPrism software.

The results from ChIP-Atlas and UCSC Genome Browser revealed that there is significant epigenetic shift of CEMIP at promoter region affected by 11-zinc finger protein or CCCTC-binding factor (CTCF). The results from RT-qPCR confirmed the successful knock-down and overexpression (Figure 1A and Figure 1B). The knock-down displayed cytotoxic effects against cancer cells (p < 0.05) while the overexpression of CEMIP increased cancer cells proliferation (p < 0.05) (Figure 1C). Moreover, cancer cells form less aggregation (3D spheroid) after si-CEMIP but better 3D structure in OE (Figure 1D). Thus, we confirmed that CEMIP drives tumor metastasis and 3D spheroid formation in castration-resistant prostate cancer cell lines.

Our investigations provide compelling and novel evidence that CEMIP has role as oncogene in androgen-resistant prostate cancer. Overall, our outcomes reveal that CEMIP may have potential as a future therapeutic target in prostate cancer.