Calcium (Ca²⁺) signaling has a major role in regulating a wide range of cellular mechanisms, including gene expression, proliferation, metabolism, cell death, muscle contraction, among others. Recent evidence suggests that ~ 1600 genes are related to the Ca²⁺ signaling. Some of these genes’ expression is altered in several pathological conditions, including different cancer types, and epigenetic mechanisms are involved. However, their expression and regulation in hepatocellular carcinoma (HCC) and the liver are barely known. Here, we aimed to explore the expression of genes involved in the Ca²⁺-signaling in HCC, liver regeneration, and hepatocyte differentiation, and whether their expression is regulated by epigenetic mechanisms such as DNA methylation and histone posttranslational modifications (HPM). Results show that several Ca²⁺-signaling genes’ expression is altered in HCC samples; among these, a subset of twenty-two correlate with patients’ survival. DNA methylation correlates with eight of these genes’ expression, and Guadecitabine, a hypomethylating agent, regulates the expression of seven down-regulated and three up-regulated genes in HepG2 cells. The down-regulated genes displayed a marked decrease of euchromatin histone marks, whereas up-regulated genes displayed gain in these marks. Additionally, the expression of these genes is modulated during liver regeneration and showed similar profiles between in vitro differentiated hepatocytes and liver-derived hepatocytes. In conclusion, some components of the Ca²⁺-signaling are altered in HCC and displayed a correlation with patients’ survival. DNA methylation and HMP are an attractive target for future investigations to regulate their expression. Ca²⁺-signaling could be an important regulator of cell proliferation and differentiation in the liver.

钙 (Ca ²⁺ ) 信号传导在调节多种细胞机制中发挥着重要作用，包括基因表达、增殖、代谢、细胞死亡、肌肉收缩等。最近的证据表明约 1600 个基因与 Ca ²⁺信号传导相关。其中一些基因的表达在多种病理条件下发生改变，包括不同的癌症类型，并且涉及表观遗传机制。然而，它们在肝细胞癌（HCC）和肝脏中的表达和调控却鲜为人知。在这里，我们的目的是探讨HCC、肝再生和肝细胞分化中Ca ²⁺信号传导相关基因的表达，以及它们的表达是否受到DNA甲基化和组蛋白翻译后修饰(HPM)等表观遗传机制的调节。结果表明，HCC 样本中多个 Ca ²⁺信号基因的表达发生了改变；其中，有二十二个子集与患者的生存相关。 DNA 甲基化与其中 8 个基因的表达相关，而瓜德西他滨（一种低甲基化剂）可调节 HepG2 细胞中 7 个下调基因和 3 个上调基因的表达。下调基因显示常染色质组蛋白标记显着减少，而上调基因显示这些标记增加。此外，这些基因的表达在肝再生过程中受到调节，并且在体外分化的肝细胞和肝源性肝细胞之间显示出相似的特征。总之，Ca ²⁺信号传导的某些成分在 HCC 中发生改变，并与患者的生存率相关。 DNA 甲基化和 HMP 是未来研究调节其表达的有吸引力的目标。 Ca ²⁺信号传导可能是肝脏细胞增殖和分化的重要调节因子。