GARS is implicated in poor survival and immune infiltration of hepatocellular carcinoma

Objective: 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.

Methods: 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.

Results: 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.

Conclusion: Our study indicates that GARS is a promising prognostic and therapeutic marker in HCC and might provide new directions and strategies for HCC treatment.