METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma Cells
Background: Gliomas are aggressive brain tumors known for their poor prognosis and resistance to standard treatment options. Ferroptosis is an iron-dependent form of regulated cell death that has emerged as a promising target for cancer treatment. This study examined how the methy...
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IMR Press
2025-02-01
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| Series: | Frontiers in Bioscience-Landmark |
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| Online Access: | https://www.imrpress.com/journal/FBL/30/2/10.31083/FBL25718 |
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| author | Hongjun Liu Shasha Tan Zhenyu Zhao Xiaoping Tang Zhou Li Jian Qi |
| author_facet | Hongjun Liu Shasha Tan Zhenyu Zhao Xiaoping Tang Zhou Li Jian Qi |
| author_sort | Hongjun Liu |
| collection | DOAJ |
| description | Background: Gliomas are aggressive brain tumors known for their poor prognosis and resistance to standard treatment options. Ferroptosis is an iron-dependent form of regulated cell death that has emerged as a promising target for cancer treatment. This study examined how the methyltransferase-like 3/YTH domain family protein 1 (METTL3/YTHDF1) axis influences ferroptosis and glioma progression by stabilizing mitochondrial carrier homolog 2 (MTCH2) messenger RNA (mRNA). Methods: MTCH2 expression in glioma tissues and cell lines was evaluated through quantitative real-time polymerase chain reaction (PCR) and western blot analyses. To assess the effects of MTCH2 knockdown and overexpression on glioma cell functions, we performed a series of functional assays, including cell viability, colony formation, and measurements of lipid reactive oxygen species (lipid ROS) and malondialdehyde (MDA) levels. Additionally, we conducted RNA immunoprecipitation (RIP) and RNA stability assays to explore the underlying mechanisms governing the interaction between METTL3, YTHDF1, and the stability of MTCH2 mRNA. Results: MTCH2 was significantly upregulated in glioma tissues and cell lines. Silencing of MTCH2 resulted in decreased glioma cell proliferation and induced ferroptosis, as evidenced by increased lipid peroxidation and ROS accumulation. Conversely, overexpression of MTCH2 enhanced glioma cell survival and reduced ferroptosis. METTL3-mediated N6-methyladenosine (m6A) modification enhanced MTCH2 mRNA stability by enabling YTHDF1 to bind and protect the modified mRNA from degradation. Conclusion: The METTL3/YTHDF1/MTCH2 axis plays a critical role in glioma progression by inhibiting ferroptosis and promoting tumor cell survival. Targeting this pathway may provide a new and effective treatment strategy for glioma patients. |
| format | Article |
| id | doaj-art-58cc4924a06d48898cb56fa37caae23f |
| institution | OA Journals |
| issn | 2768-6701 |
| language | English |
| publishDate | 2025-02-01 |
| publisher | IMR Press |
| record_format | Article |
| series | Frontiers in Bioscience-Landmark |
| spelling | doaj-art-58cc4924a06d48898cb56fa37caae23f2025-08-20T02:00:29ZengIMR PressFrontiers in Bioscience-Landmark2768-67012025-02-013022571810.31083/FBL25718S2768-6701(24)01602-2METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma CellsHongjun Liu0Shasha Tan1Zhenyu Zhao2Xiaoping Tang3Zhou Li4Jian Qi5Department of Neurosurgery, The Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Neurosurgery, The Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Neurosurgery, The Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Neurosurgery, The Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Neurosurgery, The Affiliated Nanchong Central Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaDepartment of Neurosurgery, The Affiliated Hospital of North Sichuan Medical College, 637000 Nanchong, Sichuan, ChinaBackground: Gliomas are aggressive brain tumors known for their poor prognosis and resistance to standard treatment options. Ferroptosis is an iron-dependent form of regulated cell death that has emerged as a promising target for cancer treatment. This study examined how the methyltransferase-like 3/YTH domain family protein 1 (METTL3/YTHDF1) axis influences ferroptosis and glioma progression by stabilizing mitochondrial carrier homolog 2 (MTCH2) messenger RNA (mRNA). Methods: MTCH2 expression in glioma tissues and cell lines was evaluated through quantitative real-time polymerase chain reaction (PCR) and western blot analyses. To assess the effects of MTCH2 knockdown and overexpression on glioma cell functions, we performed a series of functional assays, including cell viability, colony formation, and measurements of lipid reactive oxygen species (lipid ROS) and malondialdehyde (MDA) levels. Additionally, we conducted RNA immunoprecipitation (RIP) and RNA stability assays to explore the underlying mechanisms governing the interaction between METTL3, YTHDF1, and the stability of MTCH2 mRNA. Results: MTCH2 was significantly upregulated in glioma tissues and cell lines. Silencing of MTCH2 resulted in decreased glioma cell proliferation and induced ferroptosis, as evidenced by increased lipid peroxidation and ROS accumulation. Conversely, overexpression of MTCH2 enhanced glioma cell survival and reduced ferroptosis. METTL3-mediated N6-methyladenosine (m6A) modification enhanced MTCH2 mRNA stability by enabling YTHDF1 to bind and protect the modified mRNA from degradation. Conclusion: The METTL3/YTHDF1/MTCH2 axis plays a critical role in glioma progression by inhibiting ferroptosis and promoting tumor cell survival. Targeting this pathway may provide a new and effective treatment strategy for glioma patients.https://www.imrpress.com/journal/FBL/30/2/10.31083/FBL25718ferroptosism6a rna methylationglioma |
| spellingShingle | Hongjun Liu Shasha Tan Zhenyu Zhao Xiaoping Tang Zhou Li Jian Qi METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma Cells Frontiers in Bioscience-Landmark ferroptosis m6a rna methylation glioma |
| title | METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma Cells |
| title_full | METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma Cells |
| title_fullStr | METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma Cells |
| title_full_unstemmed | METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma Cells |
| title_short | METTL3/YTDHF1 Stabilizes MTCH2 mRNA to Regulate Ferroptosis in Glioma Cells |
| title_sort | mettl3 ytdhf1 stabilizes mtch2 mrna to regulate ferroptosis in glioma cells |
| topic | ferroptosis m6a rna methylation glioma |
| url | https://www.imrpress.com/journal/FBL/30/2/10.31083/FBL25718 |
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