National Clinical Research Center for Geriatric Disorders, Xiangya Hospital, Central South University, Changsha, China.
Research Center of Carcinogenesis and Targeted Therapy, Xiangya Hospital, Central South University, Changsha, China.
Front Immunol. 2021 Apr 2;12:636614. doi: 10.3389/fimmu.2021.636614. eCollection 2021.
The Na+/K+-ATPase (NKA), has been proposed as a signal transducer involving various pathobiological processes, including tumorigenesis. However, the clinical relevance of NKA in hepatocellular carcinoma (HCC) has not been well studied. This study revealed the upregulation of mRNA of ATP1A1, ATP1B1, and ATP1B3 in HCC using TCGA, ICGC, and GEO database. Subsequently, ATP1B3 was demonstrated as an independent prognostic factor of overall survival (OS) of HCC. To investigate the potential mechanisms of ATP1B3 in HCC, we analyzed the co-expression network using LinkedOmics and found that ATP1B3 co-expressed genes were associated with immune-related biological processes. Furthermore, we found that ATP1B3 was correlated immune cell infiltration and immune-related cytokines expression in HCC. The protein level of ATP1B3 was also validated as a prognostic significance and was correlated with immune infiltration in HCC using two proteomics datasets. Finally, functional analysis revealed that ATP1B3 was increased in HCC cells and tissues, silenced ATP1B3 repressed HCC cell proliferation, migration, and promoted HCC cell apoptosis and epithelial to mesenchymal transition (EMT). In conclusion, these findings proved that ATP1B3 could be an oncogene and it was demonstrated as an independent prognostic factor and correlated with immune infiltration in HCC, revealing new insights into the prognostic role and potential immune regulation of ATP1B3 in HCC progression and provide a novel possible therapeutic strategy for HCC.
钠钾泵（NKA）已被提出作为一种涉及多种病理生理过程的信号转导物，包括肿瘤发生。然而，NKA 在肝细胞癌（HCC）中的临床相关性尚未得到很好的研究。本研究使用 TCGA、ICGC 和 GEO 数据库揭示了 HCC 中 ATP1A1、ATP1B1 和 ATP1B3 mRNA 的上调。随后，ATP1B3 被证明是 HCC 总生存期（OS）的独立预后因素。为了研究 ATP1B3 在 HCC 中的潜在机制，我们使用 LinkedOmics 分析了共表达网络，发现 ATP1B3 共表达基因与免疫相关的生物过程有关。此外，我们发现 ATP1B3 与 HCC 中的免疫细胞浸润和免疫相关细胞因子表达相关。使用两个蛋白质组学数据集，还验证了 ATP1B3 的蛋白水平作为预后意义，并与 HCC 中的免疫浸润相关。最后，功能分析表明，ATP1B3 在 HCC 细胞和组织中增加，沉默 ATP1B3 抑制 HCC 细胞增殖、迁移，并促进 HCC 细胞凋亡和上皮间质转化（EMT）。总之，这些发现证明 ATP1B3 可以是一种癌基因，它被证明是 HCC 中的一个独立预后因素，并与免疫浸润相关，揭示了 ATP1B3 在 HCC 进展中的预后作用和潜在免疫调节的新见解，并为 HCC 提供了一种新的可能的治疗策略。
