Department of Radiology, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
Department of Interventional Surgery Center, Xijing Hospital, Fourth Military Medical University, Xi'an, Shaanxi, China.
BMC Cancer. 2024 Aug 27;24(1):1056. doi: 10.1186/s12885-024-12807-4.
The regulator of calcineurin 1 (RCAN1) is expressed in multiple organs, including the heart, liver, brain, and kidney, and is closely linked to the pathogenesis of cardiovascular diseases, Down syndrome, and Alzheimer's disease. It is also implicated in the development of various organ tumors; however, its potential role in hepatocellular carcinoma (HCC) remains poorly understood. Therefore, the objective of this study was to investigate the potential mechanisms of RCAN1 in HCC through bioinformatics analysis.
We conducted a joint analysis based on the NCBI and TCGA databases, integrating both bulk transcriptome and single-cell analyses to examine the principal biological functions of RCAN1 in HCC, as well as its roles related to phenotype, metabolism, and cell communication. Subsequently, an RCAN1-overexpressing cell line was established, and the effects of RCAN1 on tumor cells were validated through in vitro experiments. Moreover, we endeavored to identify potential related drugs using molecular docking and molecular dynamics simulations.
The expression of RCAN1 was found to be downregulated in 19 types of cancer tissues and upregulated in 11 types of cancer tissues. Higher levels of RCAN1 expression were associated with improved patient survival. RCAN1 was predominantly expressed in hepatocytes, macrophages, endothelial cells, and monocytes, and its high expression not only closely correlated with the distribution of cells related to the HCC phenotype but also with the distribution of HCC cells themselves. Additionally, Rcan1 may directly or indirectly participate in metabolic pathways such as alanine, aspartate, and glutamate metabolism, as well as butanoate metabolism, thereby influencing tumor cell proliferation and migration. In vitro experiments confirmed that RCAN1 overexpression promoted apoptosis while inhibiting proliferation and invasion of HCC cells. Through molecular docking of 1615 drugs, we screened brompheniramine as a potential target drug and verified our results by molecular dynamics.
In this study, we revealed the relationship between RCAN1 and HCC through bioinformatics methods, verified that RCAN1 can affect the progress of the disease through experiments, and finally identified potential therapeutic drugs through drug molecular docking and molecular dynamics.
钙调神经磷酸酶 1 调节因子（RCAN1）在多种器官中表达，包括心脏、肝脏、大脑和肾脏，与心血管疾病、唐氏综合征和阿尔茨海默病的发病机制密切相关。它也与各种器官肿瘤的发展有关；然而，其在肝细胞癌（HCC）中的潜在作用仍知之甚少。因此，本研究旨在通过生物信息学分析探讨 RCAN1 在 HCC 中的潜在机制。
我们基于 NCBI 和 TCGA 数据库进行联合分析，整合批量转录组和单细胞分析，研究 RCAN1 在 HCC 中的主要生物学功能，以及其与表型、代谢和细胞通讯相关的作用。随后，建立了 RCAN1 过表达细胞系，并通过体外实验验证了 RCAN1 对肿瘤细胞的影响。此外，我们还尝试使用分子对接和分子动力学模拟来识别潜在的相关药物。
RCAN1 的表达在 19 种癌症组织中下调，在 11 种癌症组织中上调。RCAN1 表达水平较高与患者生存改善相关。RCAN1 主要在肝细胞、巨噬细胞、内皮细胞和单核细胞中表达，其高表达不仅与与 HCC 表型相关的细胞分布密切相关，还与 HCC 细胞本身的分布密切相关。此外，Rcan1 可能直接或间接参与丙氨酸、天冬氨酸和谷氨酸代谢以及丁酸盐代谢等代谢途径，从而影响肿瘤细胞的增殖和迁移。体外实验证实，RCAN1 过表达可促进 HCC 细胞凋亡，抑制其增殖和侵袭。通过对 1615 种药物进行分子对接，我们筛选出溴苯那敏作为一种潜在的靶向药物，并通过分子动力学验证了我们的结果。
本研究通过生物信息学方法揭示了 RCAN1 与 HCC 之间的关系，通过实验验证了 RCAN1 可影响疾病的进展，并通过药物分子对接和分子动力学最终确定了潜在的治疗药物。
