Methionyl-tRNA synthetase 1 participates in hepatocellular carcinoma and its regulated gene profile possesses potent prognostic ability.

BACKGROUND: Hepatocellular carcinoma (HCC) is a significant global health challenge with rising incidence rates and poor prognoses. Aminoacyl-tRNA synthetases (ARSs) are important regulators implicated in the occurrence and progression of several cancers. However, their specific function in HCC remains unclear, and ARSs-related prognostic factors for patient stratification are lacking. AIM: To investigate the ARSs-related mechanisms of HCC and establish an effective prognostic risk model for stratifying patients with HCC. METHODS: We screened ARSs genes of interest using differential gene expression, mutation, and survival analysis. Western blot and Immunohistochemistry were used to analyze MARS1 expression in the liver tissues of patients with HCC. Functional studies, including CCK-8 cell viability assay, EdU cell proliferation assay, cell cycle assays, Transwell migration and invasion assays, and in vivo tumor xenograft models, were conducted to comprehensively elucidate the specific role of MARS1 in HCC. Moreover, the MARS1-related prognostic score (MRPS) was established by LASSO regression and Cox regression analysis in The Cancer Genome Atlas-HCC and GSE14520 cohorts. Patients' immunotherapy and chemotherapy responses were predicted by immunomicroenvironment and drug susceptibility analysis in both subgroups. RESULTS: MARS1 was selected as a target gene from a series of ARSs genes, with markedly higher expression observed in HCC tissues compared to adjacent non-cancerous tissues. Silencing MARS1 considerably impeded the proliferation, migration, invasion, and tumorigenic abilities of HCC cells in vitro and in vivo. Moreover, high MRPSs were associated with poor overall survival, altered infiltration of T cells, macrophages, monocytes, elevated immune checkpoint expression (PD-L1, CTLA4, LAG3), and reduced drug sensitivity in HCC. CONCLUSION: MARS1 promotes HCC development and represents a potential therapeutic target for HCC management. Furthermore, MRPS serves as an independent prognostic factor for survival and a predictor of tumor treatment response.