结直肠癌 (CRC) 是全球癌症相关死亡的主要原因之一。细胞外 ATP (e-ATP) 和嘌呤能受体 (P2R) 在 CRC 增殖和进展中发挥着核心作用。人们越来越认识到人类抗原 R (HuR) 对于癌症相关基因的表达至关重要。目前的研究表明，ATP 可以通过诱导 HuR 核质穿梭和随后癌症相关基因的表达来介导 CRC（Caco-2 细胞）进展，这一结果主要通过 P2R 受体介导。还值得注意的是，使用二氢丹参酮 I (DHTS) 抑制 HuR 活性可防止癌症相关基因表达以及随后由 ATP 诱导的 CRC（Caco-2 细胞）进展。细胞周期蛋白A2/细胞周期蛋白依赖性激酶2（CDK2）、Bcl-2、ProT-α、缺氧诱导因子1-α（HIF1-α）、血管内皮生长因子A（VEGF-A）、转化生长因子的表达在 PPADS（非选择性 P2R 拮抗剂）或 DHTS 存在下，ATP 诱导的 β (TGF-β) 和基质金属肽酶 9 (MMP-9) 显着降低。此外，在 PPADS 或 DHTS 或选择性 CDK-2 抑制剂 (Roscovitine) 或选择性 Bcl-2 抑制剂 (ABT-263) 存在的情况下，e-ATP 诱导的 Caco-2 细胞增殖以及细胞存活率大大降低。此外，我们发现 MMP-9 对于 e-ATP 诱导的 Caco-2 细胞迁移至关重要，选择性 MMP-9 抑制剂（Marimastat）存在下细胞迁移明显减少就证明了这一点。总的来说，这些数据表明，ATP 通过 P2R 激活可以诱导 HuR 核质穿梭，从而转化为癌症相关基因表达的增加以及随后的细胞增殖和进展。© 2024。作者。

One of the leading causes of cancer-related deaths worldwide is colorectal cancer (CRC). Extracellular ATP (e-ATP) and purinergic receptors (P2R) play a central role in CRC proliferation and progression. Human antigen R (HuR) is becoming more and more understood to be essential for the expression of genes linked to cancer. The current study demonstrates that ATP can mediate CRC (Caco-2 cells) progression via induction of HuR nucleocytoplasmic shuttling and subsequent expression of cancer-related genes, a consequence mostly mediated via the P2R receptor. It was also noted that suppression of HuR activity by using dihydrotanshinone I (DHTS) prevents cancer-related gene expression and subsequent CRC (Caco-2 cells) progression induced by ATP. The expression of cyclin A2/cyclin-dependent kinase 2 (CDK2), Bcl-2, ProT-α, hypoxia-inducible factor1-α (HIF1-α), vascular endothelial growth factor A (VEGF-A), transforming growth factor-β (TGF-β) and matrix metallopeptidase 9 (MMP-9) induced by ATP were highly reduced in the presence of either PPADS (non-selective P2R antagonist) or DHTS. In addition, e-ATP-induced Caco-2 cell proliferation as well as cell survival were highly reduced in the presence of either PPADS or DHTS or selective CDK-2 inhibitor (Roscovitine) or selective Bcl-2 inhibitor (ABT-263). Furthermore, it was found that MMP-9 is critical for Caco-2 cells migration induced by e-ATP as demonstrated by a clear reduction in cells migration in the presence of a selective MMP-9 inhibitor (Marimastat). Collectively, these data demonstrate that ATP through P2R activation can induce HuR nucleocytoplasmic shuttling that could be translated into an increase in cancer-related genes expression and subsequent, cell proliferation and progression.© 2024. The Author(s).