Depletion of P2X4 receptors alleviates prostate cancer bone metastasis through reducing cancer cell invasiveness and enhancing cell adhesion activities

The P2X4 receptor (P2X4R) is a receptor for ATP that is highly expressed in many cancer types including prostate cancer and is positively associated with tumourigenesis. To understand the role of P2X4R in prostate cancer bone metastasis gene P2RX4 was knocked out in human prostate cancer PC3 cells using the CRISPR/Cas9 system. Animal studies demonstrated that targeting P2X4R suppresses the process of tumour bone metastasis. RNA-seq was performed to understand the further mechanism for P2X4R deficiency correlated reduction in prostate cancer tumourigenicity. The results demonstrated that P2X4R deficiency in PC3 cells caused dramatically up-regulate the anti-tumour genes (CLDN18, ADAMTS12 and PRB2), and it also significantly increased cell adhesion function and characteristic of the epithelia gene (CLDN18), which may inhibit cancer cell invasion and delay the process of PCa bone metastasis. These findings provide important insights into the underlying biology of P2X4R and prostate cancer progression. Overall design: Knockouting out P2X4R in prostate cancer cell line PC3 using CRISPR/Cas9. Comparative gene expression profiling analysis of RNA-seq data for PC3 WT and P2X4R knockout.