Metabolic reprogramming is a major feature of cancer, and aerobic glycolysis is one of the most widely studied metabolic reprogramming processes. Acidic ribosome protein P2 (RPLP2) is associated with both tumorigenesis and endoplasmic reticulum stress. However, limited knowledge exists regarding the role of RPLP2 in hepatocellular carcinoma (HCC) progression. In the present study, we observed a significant upregulation of RPLP2 in HCC tissues. Moreover, RPLP2 expression is closely correlated with patient prognosis and survival. The subsequent experimental validation demonstrated that RPLP2 exerted a regulatory effect on the expression of glycolytic enzymes and lactate production, thereby facilitating HCC cell proliferation. Mechanistically, the PI3K/AKT signalling pathway was found to play an important role in the regulation of hypoxia-inducible factor-1α (HIF-1α)-mediated aerobic glycolysis and cell growth. RPLP2 activates TLR4 on the surface of HCC cells and the downstream PI3K/AKT pathway through autocrine signalling. This activation then facilitates the entry of HIF-1α into the nucleus, enabling it to fulfil its transcriptional function. In conclusion, our findings suggested that RPLP2 induces a metabolic shift towards aerobic glycolysis and facilitates the progression of HCC through TLR4-dependent activation of the PI3K/AKT/HIF-1α pathway. Our study revealed the novel mechanism by which the ribosomal protein RPLP2 regulates glycolysis to promote HCC progression. These findings may offer a potential therapeutic target for HCC treatment.

代谢重编程是癌症的主要特征，有氧糖酵解是研究最广泛的代谢重编程过程之一。酸性核糖体蛋白 P2 (RPLP2) 与肿瘤发生和内质网应激有关。然而，关于 RPLP2 在肝细胞癌 (HCC) 进展中的作用的知识有限。在本研究中，我们观察到 HCC 组织中 RPLP2 显着上调。此外，RPLP2表达与患者预后和生存密切相关。随后的实验验证表明，RPLP2对糖酵解酶的表达和乳酸的产生发挥调节作用，从而促进HCC细胞增殖。从机制上讲，PI3K/AKT 信号通路被发现在调节缺氧诱导因子 1α (HIF-1α) 介导的有氧糖酵解和细胞生长中发挥重要作用。 RPLP2 通过自分泌信号激活 HCC 细胞表面的 TLR4 和下游 PI3K/AKT 通路。这种激活随后促进 HIF-1α 进入细胞核，使其能够履行其转录功能。总之，我们的研究结果表明，RPLP2 诱导代谢向有氧糖酵解转变，并通过 TLR4 依赖性激活 PI3K/AKT/HIF-1α 途径促进 HCC 的进展。我们的研究揭示了核糖体蛋白 RPLP2 调节糖酵解促进 HCC 进展的新机制。这些发现可能为 HCC 治疗提供潜在的治疗靶点。