Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells
Abstract The roles of RNA m6A modification in carcinogenesis have attracted much interest recently. However, the dysregulation of RNA m6A regulators (writers, readers, and erasers) in nasopharyngeal carcinoma (NPC) has never been reported. In this study, we showed that METTL3, one of the writers, wa...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2020-11-01
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| Series: | Kaohsiung Journal of Medical Sciences |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/kjm2.12266 |
| _version_ | 1818870846816518144 |
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| author | Zhi‐Feng Liu Jing Yang Shu‐Pei Wei Xing‐Gu Luo Qing‐Shan Jiang Tao Chen Yong‐Qian Gong |
| author_facet | Zhi‐Feng Liu Jing Yang Shu‐Pei Wei Xing‐Gu Luo Qing‐Shan Jiang Tao Chen Yong‐Qian Gong |
| author_sort | Zhi‐Feng Liu |
| collection | DOAJ |
| description | Abstract The roles of RNA m6A modification in carcinogenesis have attracted much interest recently. However, the dysregulation of RNA m6A regulators (writers, readers, and erasers) in nasopharyngeal carcinoma (NPC) has never been reported. In this study, we showed that METTL3, one of the writers, was upregulated in NPC. Functional studies revealed that METTL3 promoted the migration and invasion of NPC cells. However, METTL3 knockdown reversed this effect and inhibited the migration, invasion and metastasis of NPC cells. METTL3 activated the luciferase activity of TOPflash (a reporter for beta‐catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of beta‐catenin/TCF target genes vimentin and N‐cadherin, which are two regulators of epithelial‐mesenchymal transition. Moreover, dominant negative beta‐catenin blocked the migration and invasion of NPC cells. Further mechanistic studies showed that METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. Moreover, Tankyrase overexpression abrogated the repressive effects of METTL3 silencing on the migration of NPC cells. Collectively, our study demonstrates the oncogenic roles of METTL3 in NPC, and suggests that METTL3 might be a therapeutic target for NPC. |
| first_indexed | 2024-12-19T12:13:31Z |
| format | Article |
| id | doaj.art-c3e287640cc44aea85ec235d5cc4b9bf |
| institution | Directory Open Access Journal |
| issn | 1607-551X 2410-8650 |
| language | English |
| last_indexed | 2024-12-19T12:13:31Z |
| publishDate | 2020-11-01 |
| publisher | Wiley |
| record_format | Article |
| series | Kaohsiung Journal of Medical Sciences |
| spelling | doaj.art-c3e287640cc44aea85ec235d5cc4b9bf2022-12-21T20:22:05ZengWileyKaohsiung Journal of Medical Sciences1607-551X2410-86502020-11-01361189590310.1002/kjm2.12266Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cellsZhi‐Feng Liu0Jing Yang1Shu‐Pei Wei2Xing‐Gu Luo3Qing‐Shan Jiang4Tao Chen5Yong‐Qian Gong6Department of Otorhinolaryngology The First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaDepartment of Gastroenterology The First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaDepartment of Otorhinolaryngology The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong Province ChinaDepartment of Otorhinolaryngology The First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaDepartment of Otorhinolaryngology The First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaDepartment of Otorhinolaryngology The First Affiliated Hospital of Guangzhou Medical University Guangzhou Guangdong Province ChinaDepartment of Otorhinolaryngology The First Affiliated Hospital of University of South China Hengyang Hunan Province ChinaAbstract The roles of RNA m6A modification in carcinogenesis have attracted much interest recently. However, the dysregulation of RNA m6A regulators (writers, readers, and erasers) in nasopharyngeal carcinoma (NPC) has never been reported. In this study, we showed that METTL3, one of the writers, was upregulated in NPC. Functional studies revealed that METTL3 promoted the migration and invasion of NPC cells. However, METTL3 knockdown reversed this effect and inhibited the migration, invasion and metastasis of NPC cells. METTL3 activated the luciferase activity of TOPflash (a reporter for beta‐catenin/TCF signaling), and downregulation of METTL3 inhibited the expression of beta‐catenin/TCF target genes vimentin and N‐cadherin, which are two regulators of epithelial‐mesenchymal transition. Moreover, dominant negative beta‐catenin blocked the migration and invasion of NPC cells. Further mechanistic studies showed that METTL3 silencing decreased the m6A methylation and total mRNA levels of Tankyrase, a negative regulator of axin. Moreover, Tankyrase overexpression abrogated the repressive effects of METTL3 silencing on the migration of NPC cells. Collectively, our study demonstrates the oncogenic roles of METTL3 in NPC, and suggests that METTL3 might be a therapeutic target for NPC.https://doi.org/10.1002/kjm2.12266beta‐catenincell motilityMETTL3nasopharyngeal carcinomaTankyrase |
| spellingShingle | Zhi‐Feng Liu Jing Yang Shu‐Pei Wei Xing‐Gu Luo Qing‐Shan Jiang Tao Chen Yong‐Qian Gong Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells Kaohsiung Journal of Medical Sciences beta‐catenin cell motility METTL3 nasopharyngeal carcinoma Tankyrase |
| title | Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells |
| title_full | Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells |
| title_fullStr | Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells |
| title_full_unstemmed | Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells |
| title_short | Upregulated METTL3 in nasopharyngeal carcinoma enhances the motility of cancer cells |
| title_sort | upregulated mettl3 in nasopharyngeal carcinoma enhances the motility of cancer cells |
| topic | beta‐catenin cell motility METTL3 nasopharyngeal carcinoma Tankyrase |
| url | https://doi.org/10.1002/kjm2.12266 |
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