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Mutant NPM1-Regulated FTO-Mediated m 6 A Demethylation Promotes Leukemic Cell Survival via PDGFRB/ERK Signaling Axis.
- Source :
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Frontiers in oncology [Front Oncol] 2022 Feb 08; Vol. 12, pp. 817584. Date of Electronic Publication: 2022 Feb 08 (Print Publication: 2022). - Publication Year :
- 2022
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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.<br />Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.<br /> (Copyright © 2022 Xiao, Lei, Ren, Peng, Jing, Jiang, Huang, Tao, Lin, Yang, Sun, Tang, Wei, Yang and Zhang.)
Details
- Language :
- English
- ISSN :
- 2234-943X
- Volume :
- 12
- Database :
- MEDLINE
- Journal :
- Frontiers in oncology
- Publication Type :
- Academic Journal
- Accession number :
- 35211409
- Full Text :
- https://doi.org/10.3389/fonc.2022.817584