Abstract
Gastric cancer (GC) is the fifth most common malignancy and the third leading cause of cancer-related mortality worldwide. Methionyl-tRNA synthetase 2 (Mars2) has been suggested as a biomarker indicating poor prognosis of cancers. This study focuses on the function of Mars2 in GC and the responsible molecules. Mars2 was highly expressed in GC patients according to a transcriptome analysis and the data from the public database, and its high expression was confirmed in the acquired GC cell lines. Downregulation of Mars2 significantly weakened the proliferation, resistance to death, migration and invasion of GC cells. The H3K4me3 modification level was increased in the promoter region of Mars2, which was attributed to reduced abundance of lysine demethylase 5D (KDM5D) in the Mars2 promoter. MicroRNA (miR)-4661-5p was identified as an upstream regulator of KDM5D. Downregulation of miR-4661-5p led to an increase in the expression of KDM5D while a decline in the expression of Mars2, which reduced the malignant behaviors of GC cells; however, the malignant behaviors of GC cells was restored after further inhibition of KDM5D. To conclude, this study suggested that increased Mars2 expression upon miR-4661-5p-mediated KDM5D downregulation is correlated with malignant degree of GC cells.