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Effect of depletion of METTL3 or METTL14 on gene expression in human K562 cell line, a model of chronic myeloid leukemia in the acute myeloid blast phase

GSE282987 Homo sapiens Expression profiling by high throughput sequencing 6 samples Submitted 2025/02/22 Platform GPL18573
Summary
N6-methyladenosine (m6A) RNA methylation is a significant epigenetic modification in mammalian mRNAs, crucial for tumorigenesis and development. Our study shows that the methyltransferases METTL3 and METTL14 are highly expressed in acute myeloid leukemia (AML) patients, excluding those with acute promyelocytic leukemia (APL). Elevated levels of these enzymes correlate with shorter survival rates, indicating their role as adverse prognostic factors in AML. Through comprehensive analysis of RNA-seq data and subsequent experimental validation, the knockdown of METTL3 and METTL14 was found to significantly perturb the p53 signaling pathway. This alteration resulted in the upregulation of both p53 and CDKN1A (p21), as well as an extended half-life of mdm2 mRNAs. Furthermore, METTL3 influences AML cell survival by regulating the MAPK pathway through PGC-1α, which modulates ROS detoxification and acts as an oncogene. In summary, METTL3 and METTL14 are promising targets for AML treatment.
Published in
METTL3, an Independent Adverse Prognostic Factor for AML, Promotes the Development of AML by Modulating the PGC-1α-MAPK Pathway and PGC-1α-Antioxidant System Axis
Tang Y, Liu X, Ye W et al. · Cancer medicine 2025 · PMID 40171845 · doi:10.1002/cam4.70771
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Also filed as BioProject PRJNA1191411. Searching any of these in the dataset finder brings you back here.

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