Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis
Abstract Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone met...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Nature Publishing Group
2023-05-01
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| Series: | Experimental and Molecular Medicine |
| Online Access: | https://doi.org/10.1038/s12276-023-00987-1 |
| _version_ | 1797811944750579712 |
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| author | Kwangho Kim Tae Young Ryu Eunsun Jung Tae-Su Han Jinkwon Lee Seon-Kyu Kim Yu Na Roh Moo-Seung Lee Cho-Rok Jung Jung Hwa Lim Ryuji Hamamoto Hye Won Lee Keun Hur Mi-Young Son Dae-Soo Kim Hyun-Soo Cho |
| author_facet | Kwangho Kim Tae Young Ryu Eunsun Jung Tae-Su Han Jinkwon Lee Seon-Kyu Kim Yu Na Roh Moo-Seung Lee Cho-Rok Jung Jung Hwa Lim Ryuji Hamamoto Hye Won Lee Keun Hur Mi-Young Son Dae-Soo Kim Hyun-Soo Cho |
| author_sort | Kwangho Kim |
| collection | DOAJ |
| description | Abstract Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone methyltransferase SMYD2 is overexpressed in lung cancer and that knockdown of SMYD2 could reduce the rates of cell migration and invasion in lung cancer cell lines via direct downregulation of SMAD3 via SMYD2-mediated epigenetic regulation. Furthermore, using an in vitro epithelial-mesenchymal transition (EMT) system with a Transwell system, we generated highly invasive H1299 (In-H1299) cell lines and observed the suppression of metastatic features by SMYD2 knockdown. Finally, two types of in vivo studies revealed that the formation of metastatic tumors by shSMYD2 was significantly suppressed. Thus, we suggest that SMYD2 is a potential metastasis regulator and that the development of SMYD2-specific inhibitors may help to increase the efficacy of lung cancer treatment. |
| first_indexed | 2024-03-13T07:30:14Z |
| format | Article |
| id | doaj.art-27c0d4a625994a9cb996c9922caa7bad |
| institution | Directory Open Access Journal |
| issn | 2092-6413 |
| language | English |
| last_indexed | 2024-03-13T07:30:14Z |
| publishDate | 2023-05-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Experimental and Molecular Medicine |
| spelling | doaj.art-27c0d4a625994a9cb996c9922caa7bad2023-06-04T11:07:27ZengNature Publishing GroupExperimental and Molecular Medicine2092-64132023-05-0155595296410.1038/s12276-023-00987-1Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasisKwangho Kim0Tae Young Ryu1Eunsun Jung2Tae-Su Han3Jinkwon Lee4Seon-Kyu Kim5Yu Na Roh6Moo-Seung Lee7Cho-Rok Jung8Jung Hwa Lim9Ryuji Hamamoto10Hye Won Lee11Keun Hur12Mi-Young Son13Dae-Soo Kim14Hyun-Soo Cho15Korea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyDivision of Molecular Modification and Cancer Biology, National Cancer CenterDepartment of Pathology, Keimyung University School of MedicineDepartment of Biochemistry and Cell Biology, School of Medicine, Kyungpook National UniversityKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyKorea Research Institute of Bioscience and BiotechnologyAbstract Epigenetic alterations, especially histone methylation, are key factors in cell migration and invasion in cancer metastasis. However, in lung cancer metastasis, the mechanism by which histone methylation regulates metastasis has not been fully elucidated. Here, we found that the histone methyltransferase SMYD2 is overexpressed in lung cancer and that knockdown of SMYD2 could reduce the rates of cell migration and invasion in lung cancer cell lines via direct downregulation of SMAD3 via SMYD2-mediated epigenetic regulation. Furthermore, using an in vitro epithelial-mesenchymal transition (EMT) system with a Transwell system, we generated highly invasive H1299 (In-H1299) cell lines and observed the suppression of metastatic features by SMYD2 knockdown. Finally, two types of in vivo studies revealed that the formation of metastatic tumors by shSMYD2 was significantly suppressed. Thus, we suggest that SMYD2 is a potential metastasis regulator and that the development of SMYD2-specific inhibitors may help to increase the efficacy of lung cancer treatment.https://doi.org/10.1038/s12276-023-00987-1 |
| spellingShingle | Kwangho Kim Tae Young Ryu Eunsun Jung Tae-Su Han Jinkwon Lee Seon-Kyu Kim Yu Na Roh Moo-Seung Lee Cho-Rok Jung Jung Hwa Lim Ryuji Hamamoto Hye Won Lee Keun Hur Mi-Young Son Dae-Soo Kim Hyun-Soo Cho Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis Experimental and Molecular Medicine |
| title | Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis |
| title_full | Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis |
| title_fullStr | Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis |
| title_full_unstemmed | Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis |
| title_short | Epigenetic regulation of SMAD3 by histone methyltransferase SMYD2 promotes lung cancer metastasis |
| title_sort | epigenetic regulation of smad3 by histone methyltransferase smyd2 promotes lung cancer metastasis |
| url | https://doi.org/10.1038/s12276-023-00987-1 |
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