MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor (RNA-Seq)
Background Mitogen-activated protein kinase 1 (MAPK1) has independent functions of phosphorylating histones as a kinase and directly binding the promoter regions of genes to regulate gene expression as a transcription factor. Previous studies identified elevated expression of MAPK1 in human gastric cancer, which is associated with its role as a kinase, facilitating gastric cancer cell migration and invasion. However, being a transcription factor, how MAPK1 binds its target genes and whether it modulated related gene expressions in gastric cancer remains unclear.   Results Here, we integrated biochemical assays (protein interactions and chromatin immunoprecipitation (ChIP)), cellular analysis assays (cell proliferation and migration), RNA sequencing, ChIP sequencing, and clinical analysis to investigate the potential genomic recognition patterns of MAPK1 in a human gastric adenocarcinoma cell-line (AGS) and to uncover its regulatory effect on gastric cancer progression. We confirmed that MAPK1 promotes AGS cells invasion and migration by regulating the target genes in controversial directions, up-regulating seven target genes (KRT13, KRT6A, KRT81, MYH15, STARD4, SYTL4, and TMEM267) and down-regulating one gene (FGG). Among them, five genes (FGG, MYH15, STARD4, SYTL4, and TMEM267) were first associated with cancer procession, while the other three (KRT81, KRT6A, and KRT13) have been previously confirmed to be related to cancer metastasis and migration.   Conclusion Our data showed that MAPK1 binds to the promoter regions of these target genes to control their transcription, hence encouraging AGS cell motility and invasion. Our research broadened the understanding of the regulatory roles of MAPK1, enriched the knowledge of transcription factors, and provided novel candidates for cancer therapeutics. Overall design: Previous studies identified elevated expression of MAPK1 in human gastric cancer, which is associated with its role as a kinase, facilitating gastric cancer cell migration and invasion. However, being a transcription factor, how MAPK1 binds its target genes and whether it modulated related gene expressions in gastric cancer remains unclear. In the current study, we performed the integrated approaches of gene overexpression, gene knockdown, RNA sequencing (RNA-seq), and ChIP sequencing (ChIP-seq) to investigate the transcription regulatory function of MAPK1 and its effect on gastric cancer progress.