Yang Chen, Yang Xiaofeng, Liu Chenghao, Hou Jun, Chen Xueling, Wang Lianghai, Wu Xiangwei
NHC Key Laboratory of Prevention and Treatment of Central Asia High Incidence Diseases, the First Affiliated Hospital, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Key Laboratory of Xinjiang Endemic and Ethnic Diseases, Shihezi University School of Medicine, Shihezi, Xinjiang, China.
Infect Agent Cancer. 2023 May 3;18(1):27. doi: 10.1186/s13027-023-00503-0.
Glutamyl-prolyl-tRNA synthetase 1 (EPRS1) is an aminoacyl-tRNA synthase involved in the pathology of cancer and other diseases. In this study, we investigated the carcinogenic function, potential mechanism, and clinical significance of EPRS1 in human hepatocellular carcinoma (HCC).
The expression, clinical significance, and prognostic value of EPRS1 in HCC were assessed using the TCGA and GEO databases. The function of EPRS1 in HCC cells was detected by CCK-8, Transwell, and hepatosphere formation assays. Immunohistochemistry was used to explore the difference in EPRS1 levels in HCC tissues and peri-cancerous tissues. The mechanism of EPRS1 was studied using a proteomics method. Finally, cBioportal and MEXEPRSS were used to analyze the variations involved in the differential expression of EPRS1.
EPRS1 was frequently upregulated at the mRNA and protein levels in liver cancer. Increased EPRS1 correlated with shortened patient survival. EPRS1 could promote cancer cell proliferation, characteristics of cell stemness, and mobility. Mechanistically, EPRS1 played a carcinogenic role by upregulating several downstream proline-rich proteins, primarily LAMC1 and CCNB1. In addition, copy number variation could contribute to the high expression of EPRS1 in liver cancer.
Together, our data imply that enhanced EPRS1 contributes to the development of HCC by increasing the expression of oncogenes in the tumor microenvironment. EPRS1 may be a successful treatment target.
谷氨酰胺酰 - 脯氨酰 - tRNA合成酶1（EPRS1）是一种氨酰 - tRNA合成酶，参与癌症和其他疾病的病理过程。在本研究中，我们调查了EPRS1在人类肝细胞癌（HCC）中的致癌功能、潜在机制及临床意义。
使用TCGA和GEO数据库评估EPRS1在肝癌中的表达、临床意义及预后价值。通过CCK - 8、Transwell和肝球形成试验检测EPRS1在肝癌细胞中的功能。采用免疫组织化学方法探究肝癌组织和癌旁组织中EPRS1水平的差异。使用蛋白质组学方法研究EPRS1的机制。最后，利用cBioportal和MEXEPRSS分析EPRS1差异表达所涉及的变异。
EPRS1在肝癌中的mRNA和蛋白质水平经常上调。EPRS1升高与患者生存期缩短相关。EPRS1可促进癌细胞增殖、细胞干性特征及迁移能力。机制上，EPRS1通过上调几种下游富含脯氨酸的蛋白质发挥致癌作用，主要是LAMC1和CCNB1。此外，拷贝数变异可能导致EPRS1在肝癌中高表达。
总之，我们的数据表明，增强的EPRS1通过增加肿瘤微环境中癌基因的表达促进肝癌的发展。EPRS1可能是一个成功的治疗靶点。
