MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor
Document Type
Journal Article
Publication Title
BMC Cancer
Volume
23
Issue
1
PubMed ID
37817112
Publisher
Springer
School
Centre for Precision Health / School of Science
RAS ID
60691
Funders
Edith Cowan University / 13th Five-year Science and Technology Project of the Jilin Provincial Education Department
Abstract
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.
DOI
10.1186/s12885-023-11480-3
Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.
Comments
Wang, Y., Guo, Z., Tian, Y., Cong, L., Zheng, Y., Wu, Z., . . . Song, Y. (2023). MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor. BMC Cancer, 23, article 959. https://doi.org/10.1186/s12885-023-11480-3