MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor
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...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2023-10-01
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| Series: | BMC Cancer |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12885-023-11480-3 |
| _version_ | 1797559035839381504 |
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| author | Yue Wang Zheng Guo Yueli Tian Liang Cong Yulu Zheng Zhiyuan Wu Guangle Shan Yao Xia Yahong Zhu Xingang Li Ying Song |
| author_facet | Yue Wang Zheng Guo Yueli Tian Liang Cong Yulu Zheng Zhiyuan Wu Guangle Shan Yao Xia Yahong Zhu Xingang Li Ying Song |
| author_sort | Yue Wang |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-10T17:40:02Z |
| format | Article |
| id | doaj.art-980fadd79aeb47fa8ad2733129fc0537 |
| institution | Directory Open Access Journal |
| issn | 1471-2407 |
| language | English |
| last_indexed | 2024-03-10T17:40:02Z |
| publishDate | 2023-10-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Cancer |
| spelling | doaj.art-980fadd79aeb47fa8ad2733129fc05372023-11-20T09:43:44ZengBMCBMC Cancer1471-24072023-10-0123111310.1186/s12885-023-11480-3MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factorYue Wang0Zheng Guo1Yueli Tian2Liang Cong3Yulu Zheng4Zhiyuan Wu5Guangle Shan6Yao Xia7Yahong Zhu8Xingang Li9Ying Song10Gastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin UniversityCentre for Precision Health, Edith Cowan UniversityGastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin UniversityGastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin UniversityCentre for Precision Health, Edith Cowan UniversityCentre for Precision Health, Edith Cowan UniversityDepartment of Bioinformatics, Thrive BioresearchSchool of Science, Edith Cowan UniversityDepartment of Bioinformatics, Thrive BioresearchCentre for Precision Health, Edith Cowan UniversityGastroenteric Medicine and Digestive Endoscopy Center, The Second Hospital of Jilin UniversityAbstract 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.https://doi.org/10.1186/s12885-023-11480-3Gastric cancerMAPK1Bidirectional transcription factorCancer progression |
| spellingShingle | Yue Wang Zheng Guo Yueli Tian Liang Cong Yulu Zheng Zhiyuan Wu Guangle Shan Yao Xia Yahong Zhu Xingang Li Ying Song MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor BMC Cancer Gastric cancer MAPK1 Bidirectional transcription factor Cancer progression |
| title | MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor |
| title_full | MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor |
| title_fullStr | MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor |
| title_full_unstemmed | MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor |
| title_short | MAPK1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor |
| title_sort | mapk1 promotes the metastasis and invasion of gastric cancer as a bidirectional transcription factor |
| topic | Gastric cancer MAPK1 Bidirectional transcription factor Cancer progression |
| url | https://doi.org/10.1186/s12885-023-11480-3 |
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