The antagonistic effect of FTO on METTL14 promotes AKT3 m 6 A demethylation and the progression of esophageal cancer

As the most abundant modification in eukaryotic messenger RNAs (mRNAs), N -methyladenosine (m A) plays vital roles in many biological processes. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen for m A targets in esophageal can...

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Published in:Journal of cancer research and clinical oncology 2024-03, Vol.150 (3), p.131
Main Authors: Wei, Ran, Zhao, Fangfang, Kong, Lingsuo, Pu, Youguang, Li, Yuanhai, Zang, Chunbao
Format: Article
Language:English
Subjects:
Alpha-Ketoglutarate-Dependent Dioxygenase FTO - metabolism
Carcinogenesis
Cell Transformation, Neoplastic
Demethylation
Esophageal Neoplasms - metabolism
Esophageal Neoplasms - pathology
Humans
Methyltransferases - metabolism
Proto-Oncogene Proteins c-akt - metabolism
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Summary:As the most abundant modification in eukaryotic messenger RNAs (mRNAs), N -methyladenosine (m A) plays vital roles in many biological processes. Methylated RNA immunoprecipitation sequencing (MeRIP-seq) and transcriptomic RNA sequencing (RNA-seq) were used to screen for m A targets in esophageal cancer cells and patients. The role of m A 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. We found that the m A 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 m A 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 m A-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 m A-mediated tumorigenesis in esophageal cancer and could lead to the design of new therapeutic strategies.
ISSN:1432-1335