MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor

Background: The Mitogen-activated protein kinase 1 (MAPK1) has both 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 have identified elevated expression of MAPK1 in human gastric cancer, which is associated with its role as a kinase, facilitating the migration and invasion of gastric cancer cells. However, how MAPK1 binds to its target genes as a transcription factor and whether it modulates 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 different 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 previously been confirmed to be related to cancer metastasis and migration. Conclusion: Our data showed that MAPK1 can bind to the promoter regions of these target genes to control their transcription as a bidirectional transcription factor, promoting AGS cell motility and invasion. Our research has expanded the understanding of the regulatory roles of MAPK1, enriched our knowledge of transcription factors, and provided novel candidates for cancer therapeutics

Evolution of Complex Thallus Alga: Genome Sequencing of Saccharina japonica

Saccharina, as one of the most important brown algae (Phaeophyceae) with multicellular thallus, has a very remarkable evolutionary history, and globally accounts for most of the economic marine aquaculture production worldwide. Here, we present the 580.5 million base pairs of genome sequence of Saccharina japonica, whose current assembly contains 35,725 protein-coding genes. In a comparative analysis with Ectocarpus siliculosus, the integrated virus sequence suggested the genome evolutionary footprints, which derived from their co-ancestry and experienced genomic arrangements. Furthermore, the gene expansion was found to be an important strategy for functional evolution, especially with regard to extracelluar components, stress-related genes, and vanadium-dependent haloperoxidases, and we proposed a hypothesis that gene duplication events were the main driving force for the evolution history from multicellular filamentous algae to thallus algae. The sequenced Saccharina genome paves the way for further molecular studies and is useful for genome-assisted breeding of S. japonica and other related algae species

Sequence data.

<p>Sequence data.</p

Taxonomic diversity of the <i>I</i>. <i>persulcatus</i> core bacterial flora.

<p>Taxonomic diversity of the <i>I</i>. <i>persulcatus</i> core bacterial flora.</p

Kingdom classification of the three groups.

<p>Sequences that failed to be classified are assigned as other. Note that bacteria dominate in wild and R1 whereas eukaryotes become the greater majority in R8. Viruses are assigned in all groups but archaea are found present only in wild and R1.</p

On the core bacterial flora of <i>Ixodes persulcatus</i> (Taiga tick) - Fig 6

<p>Heatmap of the shared phyla (A) and genera (B) of the three groups to highlight the abundance of taxonomic classes.</p

Additional file 1 of MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor

Supplementary Material