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Mutant NPM1-Regulated FTO-Mediated m6A Demethylation Promotes Leukemic Cell Survival via PDGFRB/ERK Signaling Axis.
- Source :
- Frontiers in Oncology; 2/8/2022, Vol. 12, p1-17, 16p
- Publication Year :
- 2022
-
Abstract
- Acute myeloid leukemia (AML) with nucleophosmin 1 (NPM1) mutations exhibits distinct biological and clinical features, accounting for approximately one-third of AML. Recently, the N <superscript>6</superscript>-methyladenosine (m<superscript>6</superscript>A) RNA modification has emerged as a new epigenetic modification to contribute to tumorigenesis and development. However, there is limited knowledge on the role of m<superscript>6</superscript>A modifications in NPM1-mutated AML. In this study, the decreased m<superscript>6</superscript>A level was first detected and high expression of fat mass and obesity-associated protein (FTO) was responsible for the m<superscript>6</superscript>A suppression in NPM1-mutated AML. FTO upregulation was partially induced by NPM1 mutation type A (NPM1-mA) through impeding the proteasome pathway. Importantly, FTO promoted leukemic cell survival by facilitating cell cycle and inhibiting cell apoptosis. Mechanistic investigations demonstrated that FTO depended on its m<superscript>6</superscript>A RNA demethylase activity to activate PDGFRB/ERK signaling axis. Our findings indicate that FTO-mediated m<superscript>6</superscript>A demethylation plays an oncogenic role in NPM1-mutated AML and provide a new layer of epigenetic insight for future treatments of this distinctly leukemic entity. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 2234943X
- Volume :
- 12
- Database :
- Complementary Index
- Journal :
- Frontiers in Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 155125677
- Full Text :
- https://doi.org/10.3389/fonc.2022.817584