Hepatocellular carcinoma (HCC) is often discovered at an advanced stage, limiting treatment options and leading to poor prognosis. P2RX4, an ATP-gated ion channel, regulates calcium ion influx and participates in cell proliferation, inflammatory processes, and immune responses. However, its role in HCC remains unclear. Here, researchers investigated the expression, function, and immune effects of P2RX4 in HCC. The study showed that P2RX4 expression is elevated in HCC tissues, and its expression is associated with advanced tumor stage and poor prognosis. Silencing P2RX4 reduces tumor cell proliferation and invasion, decreases intracellular calcium ion levels, and inhibits AKT phosphorylation. Elevated P2RX4 levels were associated with increased numbers of M0 macrophages and regulatory T cells (Tregs), decreased monocyte numbers, and poor expected response to immunotherapy. Therefore, P2RX4 may promote HCC progression by enhancing calcium ion influx, activating the PI3K/AKT pathway, and weakening anti-tumor immunity. It may serve as a biomarker and therapeutic target for HCC.
To investigate the role of P2RX4 in the progression of hepatocellular carcinoma (HCC), researchers first assessed its expression levels in various HCC cell lines. Huh7 and Hep3B cells showed high P2RX4 expression levels (Figure 1A), and these two cell types were selected for subsequent gene knockdown experiments (Figure 1B). Subsequently, a series of functional experiments were conducted to evaluate the effect of P2RX4 knockdown. The CCK-8 assay showed that the proliferation capacity of P2RX4-knockdown cells was significantly reduced (Figure 1C). Similarly, the colony formation assay showed that the colony formation capacity of P2RX4-knockdown cells was significantly reduced (Figure 1D). The Transwell invasion assay showed weakened cell invasion capacity (Figure 1E). These results collectively indicate that P2RX4 enhances key malignant characteristics of HCC cells, such as increased proliferation, colony formation, and invasion, thus confirming its potential oncogenic role in HCC progression.
Figure 1. Biological functions of P2RX4 in HCC cells. (Wang J, et al., 2025)