ALYREF expression correlated with upregulated YBX1 and HIF1α, contributing to cell migration in gastric cancer

RNA 5-methylcytosine modification (m5C) plays important roles in tumorigenesis. The "readers" of m5C, such as YBX1 and ALYREF, are responsible for recognizing and binding to m5C modification sites, and then regulating RNA metabolism. To explore the mechanism of their roles in gastric cancer (GC), we examined the expression levels of YBX1 and ALYREF in GC patient tissues. It was found that YBX1 and ALYREF exhibited higher expression in GC tissues than their adjacent normal controls. To explore the biological function of YBX1 and ALYREF, the genes that bind to YBX1 and/or ALYREF underwent Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) enrichment analysis. The results showed that enriched genes were involved in cell migration. In vitro cell-based assays confirmed that both YBX1 and ALYREF enhanced the ability of cell migration in GC. Interestingly, we found that there was a significant correlation among the expression level of ALYREF and HIF1α, and the proportion of CagA-positive in GC patients, implying that helicobacter pylori (Hp) infection may relate to the upregulation of ALYREF and HIF1α. Quantitative PCR (qPCR) and prediction of transcription factor binding sites indicated that YBX1 may regulate the expression of ALYREF in GC, and perhaps YBX1 and ALYREF regulate HIF1α expression level by joint action. In summary, our results suggest that YBX1/ALYREF correlates with HIF1α and accelerates malignant progression of GC through affecting cell migration. The function mode of YBX1 and ALYREF provides a new insight for the diagnosis of GC and lays a foundation for the development of epigenetic antitumor drugs.