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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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE282987 | GEO | 2025/02/22

REPOSITORIES: GEO

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