N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma
Abstract In pancreatic cancer, methyltransferase-like 3 (METTL3), a N(6)-methyladenosine (m6A) methyltransferase, has a favorable effect on tumors and is a risk factor for patients’ prognosis. However, the details of what genes are regulated by METTL3 remain unknown. Several RNAs are methylated, and...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-15196-5 |
| _version_ | 1818235536752508928 |
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| author | Shotaro Tatekawa Keisuke Tamari Ryota Chijimatsu Masamitsu Konno Daisuke Motooka Suguru Mitsufuji Hirofumi Akita Shogo Kobayashi Yoshiki Murakumo Yuichiro Doki Hidetoshi Eguchi Hideshi Ishii Kazuhiko Ogawa |
| author_facet | Shotaro Tatekawa Keisuke Tamari Ryota Chijimatsu Masamitsu Konno Daisuke Motooka Suguru Mitsufuji Hirofumi Akita Shogo Kobayashi Yoshiki Murakumo Yuichiro Doki Hidetoshi Eguchi Hideshi Ishii Kazuhiko Ogawa |
| author_sort | Shotaro Tatekawa |
| collection | DOAJ |
| description | Abstract In pancreatic cancer, methyltransferase-like 3 (METTL3), a N(6)-methyladenosine (m6A) methyltransferase, has a favorable effect on tumors and is a risk factor for patients’ prognosis. However, the details of what genes are regulated by METTL3 remain unknown. Several RNAs are methylated, and what genes are favored in pancreatic cancer remains unclear. By epitranscriptomic analysis, we report that polo-like kinase 1 (PLK1) is an important hub gene defining patient prognosis in pancreatic cancer and that RNA methylation is involved in regulating its cell cycle-specific expression. We found that insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) binds to m6A of PLK1 3′ untranslated region and is involved in upregulating PLK1 expression and that demethylation of this site activates the ataxia telangiectasia and Rad3-related protein pathway by replicating stress and increasing mitotic catastrophe, resulting in increased radiosensitivity. This suggests that PLK1 methylation is essential for cell cycle maintenance in pancreatic cancer and is a new therapeutic target. |
| first_indexed | 2024-12-12T11:55:32Z |
| format | Article |
| id | doaj.art-7e0bd74eab3f4a91a581cff49c3255fe |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-12-12T11:55:32Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-7e0bd74eab3f4a91a581cff49c3255fe2022-12-22T00:25:12ZengNature PortfolioScientific Reports2045-23222022-06-0112112010.1038/s41598-022-15196-5N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinomaShotaro Tatekawa0Keisuke Tamari1Ryota Chijimatsu2Masamitsu Konno3Daisuke Motooka4Suguru Mitsufuji5Hirofumi Akita6Shogo Kobayashi7Yoshiki Murakumo8Yuichiro Doki9Hidetoshi Eguchi10Hideshi Ishii11Kazuhiko Ogawa12Department of Radiation Oncology, Osaka University Graduate School of MedicineDepartment of Radiation Oncology, Osaka University Graduate School of MedicineDepartment of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of MedicineDepartment of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of MedicineGenome Information Research Center, Research Institute for Microbial Diseases, Osaka UniversityDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Pathology, Kitasato University School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Gastroenterological Surgery, Osaka University Graduate School of MedicineDepartment of Medical Data Science, Center of Medical Innovation and Translational Research, Osaka University Graduate School of MedicineDepartment of Radiation Oncology, Osaka University Graduate School of MedicineAbstract In pancreatic cancer, methyltransferase-like 3 (METTL3), a N(6)-methyladenosine (m6A) methyltransferase, has a favorable effect on tumors and is a risk factor for patients’ prognosis. However, the details of what genes are regulated by METTL3 remain unknown. Several RNAs are methylated, and what genes are favored in pancreatic cancer remains unclear. By epitranscriptomic analysis, we report that polo-like kinase 1 (PLK1) is an important hub gene defining patient prognosis in pancreatic cancer and that RNA methylation is involved in regulating its cell cycle-specific expression. We found that insulin like growth factor 2 mRNA binding protein 2 (IGF2BP2) binds to m6A of PLK1 3′ untranslated region and is involved in upregulating PLK1 expression and that demethylation of this site activates the ataxia telangiectasia and Rad3-related protein pathway by replicating stress and increasing mitotic catastrophe, resulting in increased radiosensitivity. This suggests that PLK1 methylation is essential for cell cycle maintenance in pancreatic cancer and is a new therapeutic target.https://doi.org/10.1038/s41598-022-15196-5 |
| spellingShingle | Shotaro Tatekawa Keisuke Tamari Ryota Chijimatsu Masamitsu Konno Daisuke Motooka Suguru Mitsufuji Hirofumi Akita Shogo Kobayashi Yoshiki Murakumo Yuichiro Doki Hidetoshi Eguchi Hideshi Ishii Kazuhiko Ogawa N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma Scientific Reports |
| title | N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma |
| title_full | N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma |
| title_fullStr | N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma |
| title_full_unstemmed | N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma |
| title_short | N(6)-methyladenosine methylation-regulated polo-like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma |
| title_sort | n 6 methyladenosine methylation regulated polo like kinase 1 cell cycle homeostasis as a potential target of radiotherapy in pancreatic adenocarcinoma |
| url | https://doi.org/10.1038/s41598-022-15196-5 |
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