Wang Jinghui, Yang Bing, Wang Dingxue, Han Rui, Bi Zhanyang, Lin Lizhu
Department of Oncology, The First Affiliated Hospital of Guizhou University of Chinese Medicine, Guiyang 550001, PR China.
Department of Oncology, The First Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou 510405, PR China.
Cell Signal. 2022 Jun;94:110302. doi: 10.1016/j.cellsig.2022.110302. Epub 2022 Mar 7.
Hepatocellular carcinoma (HCC) is a malignant cancer with poor survival rates. Glycyl-tRNA synthetase (GARS) is a tRNA-charging enzyme that can serve as a biomarker for multiple tumors. Nevertheless, the role of GARS in HCC remains unclear.
The expression, clinical significance, prognostic value, genetic alterations, immune infiltration and histone modification of GARS in HCC were assessed using multiple databases. The role of GARS in HCC cells was also verified by CCK-8, cell cycle analysis and apoptosis assays in vitro and by a xenograft model in vivo.
GARS levels were upregulated in HCC tissues and cells. GARS was confirmed to be a prognostic factor in HCC patients and was significantly correlated with immune infiltration. Enhanced GARS expression in HCC was induced by histone modification of the GARS promotor. Functional network analysis showed that GARS and its coexpressed genes regulate the cell cycle, lysosome and spliceosome. Furthermore, we found that GARS depletion inhibited HCC cell proliferation and cell cycle progression and promoted apoptosis in vitro. GARS overexpression promoted growth, reduced xenograft apoptosis and enhanced CD206+ tumor-associated macrophage infiltration in vivo.
Our study indicates that GARS is a promising prognostic and therapeutic marker in HCC and might provide new directions and strategies for HCC treatment.
肝细胞癌（HCC）是一种生存率较低的恶性肿瘤。甘氨酰 - tRNA合成酶（GARS）是一种tRNA充电酶，可作为多种肿瘤的生物标志物。然而，GARS在HCC中的作用仍不清楚。
使用多个数据库评估GARS在HCC中的表达、临床意义、预后价值、基因改变、免疫浸润和组蛋白修饰。还通过体外CCK - 8、细胞周期分析和凋亡检测以及体内异种移植模型验证了GARS在HCC细胞中的作用。
HCC组织和细胞中GARS水平上调。GARS被证实是HCC患者的预后因素，并且与免疫浸润显著相关。HCC中GARS表达增强是由GARS启动子的组蛋白修饰诱导的。功能网络分析表明，GARS及其共表达基因调节细胞周期、溶酶体和剪接体。此外，我们发现GARS缺失在体外抑制HCC细胞增殖和细胞周期进程并促进凋亡。GARS过表达在体内促进生长、减少异种移植凋亡并增强CD206 +肿瘤相关巨噬细胞浸润。
我们的研究表明，GARS是HCC中有前景的预后和治疗标志物，可能为HCC治疗提供新的方向和策略。
