The antagonistic effect of FTO on METTL14 promotes AKT3 m6A demethylation and the progression of esophageal cancer
© 2024. The Author(s)..
BACKGROUND: As the most abundant modification in eukaryotic messenger RNAs (mRNAs), N6-methyladenosine (m6A) plays vital roles in many biological processes.
METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen for m6A targets in esophageal cancer cells and patients. The role of m6A RNA methylase in esophageal cancer was also analyzed using bioinformatics. In vitro and in vivo experiments were used to analyze gene expression and function. CCK-8, colony formation, cell apoptosis and immunofluorescence staining assays were performed to evaluate the proliferation, migration and invasion of esophageal cancer cells, respectively. Western blot analysis, RNA stability, RIP and luciferase reporter assays were performed to elucidate the underlying mechanism involved.
RESULTS: We found that the m6A demethylase FTO was significantly upregulated in esophageal cancer cell lines and patient tissues. In vivo and in vitro assays demonstrated that FTO was involved in the proliferation and apoptosis of esophageal cancer cells. Moreover, we found that the m6A methyltransferase METTL14 negatively regulates FTO function in esophageal cancer progression. FTO alone is not related to the prognosis of esophageal cancer, and its function is antagonized by METTL14. By using transcriptome-wide m6A-seq and RNA-seq assays, we revealed that AKT3 is a downstream target of FTO and acts in concert to regulate the tumorigenesis and metastasis of esophageal cancer. Taken together, these findings provide insight into m6A-mediated tumorigenesis in esophageal cancer and could lead to the design of new therapeutic strategies.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:150 |
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| Enthalten in: |
Journal of cancer research and clinical oncology - 150(2024), 3 vom: 15. März, Seite 131 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Wei, Ran [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 18.03.2024 Date Revised 13.04.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1007/s00432-024-05660-2 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369808789 |
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| 041 | |a eng | ||
| 100 | 1 | |a Wei, Ran |e verfasserin |4 aut | |
| 245 | 1 | 4 | |a The antagonistic effect of FTO on METTL14 promotes AKT3 m6A demethylation and the progression of esophageal cancer |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
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| 500 | |a Date Completed 18.03.2024 | ||
| 500 | |a Date Revised 13.04.2024 | ||
| 500 | |a published: Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2024. The Author(s). | ||
| 520 | |a BACKGROUND: As the most abundant modification in eukaryotic messenger RNAs (mRNAs), N6-methyladenosine (m6A) plays vital roles in many biological processes | ||
| 520 | |a METHODS: Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen for m6A targets in esophageal cancer cells and patients. The role of m6A RNA methylase in esophageal cancer was also analyzed using bioinformatics. In vitro and in vivo experiments were used to analyze gene expression and function. CCK-8, colony formation, cell apoptosis and immunofluorescence staining assays were performed to evaluate the proliferation, migration and invasion of esophageal cancer cells, respectively. Western blot analysis, RNA stability, RIP and luciferase reporter assays were performed to elucidate the underlying mechanism involved | ||
| 520 | |a RESULTS: We found that the m6A demethylase FTO was significantly upregulated in esophageal cancer cell lines and patient tissues. In vivo and in vitro assays demonstrated that FTO was involved in the proliferation and apoptosis of esophageal cancer cells. Moreover, we found that the m6A methyltransferase METTL14 negatively regulates FTO function in esophageal cancer progression. FTO alone is not related to the prognosis of esophageal cancer, and its function is antagonized by METTL14. By using transcriptome-wide m6A-seq and RNA-seq assays, we revealed that AKT3 is a downstream target of FTO and acts in concert to regulate the tumorigenesis and metastasis of esophageal cancer. Taken together, these findings provide insight into m6A-mediated tumorigenesis in esophageal cancer and could lead to the design of new therapeutic strategies | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a N 6-methyladenosine (m6a) | |
| 650 | 4 | |a AKT3 | |
| 650 | 4 | |a Esophageal cancer | |
| 650 | 4 | |a FTO | |
| 650 | 4 | |a METTL14 | |
| 650 | 7 | |a AKT3 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 650 | 7 | |a Alpha-Ketoglutarate-Dependent Dioxygenase FTO |2 NLM | |
| 650 | 7 | |a EC 1.14.11.33 |2 NLM | |
| 650 | 7 | |a FTO protein, human |2 NLM | |
| 650 | 7 | |a EC 1.14.11.33 |2 NLM | |
| 650 | 7 | |a Methyltransferases |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a METTL14 protein, human |2 NLM | |
| 650 | 7 | |a EC 2.1.1.- |2 NLM | |
| 650 | 7 | |a Proto-Oncogene Proteins c-akt |2 NLM | |
| 650 | 7 | |a EC 2.7.11.1 |2 NLM | |
| 700 | 1 | |a Zhao, Fangfang |e verfasserin |4 aut | |
| 700 | 1 | |a Kong, Lingsuo |e verfasserin |4 aut | |
| 700 | 1 | |a Pu, Youguang |e verfasserin |4 aut | |
| 700 | 1 | |a Li, Yuanhai |e verfasserin |4 aut | |
| 700 | 1 | |a Zang, Chunbao |e verfasserin |4 aut | |
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