FTO plays an oncogenic role in acute myeloid leukemia as a N6-methyladenosine RNA demethylase

By Zejuan Li, Hengyou Weng, R. Su, X. Weng, Zhixiang Zuo, Chenying Li, Huilin Huang, S. Nachtergaele, Lei Dong, Chao Hu and 19 more. Cancer Cell, 2016

1,299 citations recorded by the source corpus.

SUMMARY N6-methyladenosine (m6A) represents the most prevalent internal modification in mammalian mRNAs. Despite its functional importance in various fundamental bioprocesses, the studies of m6A in cancer have been limited. Here we show that FTO, as an m6A demethylase, plays a critical oncogenic role in acute myeloid leukemia (AML). FTO is highly expressed in AMLs with t(11q23)/MLL-rearrangements, t(15;17)/PML-RARA, FLT3-ITD and/or NPM1 mutations. FTO enhances leukemic oncogene-mediated cell transformation and leukemogenesis, and inhibits all-trans-retinoic acid (ATRA)-induced AML cell differentiation, through regulating expression of targets such as ASB2 and RARA by reducing m6A levels in these mRNA transcripts. Collectively, our study demonstrates the functional importance of the m6A methylation and the corresponding proteins in cancer, and provides profound insights into leukemogensis and drug response.

Subfields: Molecular Biology

View Paper: https://www.semanticscholar.org/paper/139947c344080f9dfc9ef43202e794fc9b5c700f

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In Molecular Biology

1. Chuan He
2. Samie R. Jaffrey
3. P. He
4. Kate D. Meyer
5. Hailing Shi
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7. Jianjun Chen
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Citations in the corpus

• m6A RNA Methylation Regulates the Self-Renewal and Tumorigenesis of Glioblastoma Stem Cells (2017, background): “Moreover, the role of m6A in cancer is only starting to be revealed (Zhang et al., 2016; Li et al., 2017).”
• Dynamic transcriptomic m6A decoration: writers, erasers, readers and functions in RNA metabolism (2018, background): “, luciferase reporter/mutagenesis assays and gene region-speific m(6)A qPCR) to be regulated by FTO.(91,92) The possible mechanisms underlying the phenomenon that both FTO and METTL14 play oncogenic roles in AML have been discussed.”
• RNA N6-methyladenosine modification in cancers: current status and perspectives (2018, background): “, MLL-AF9) mediated transformation of normal hematopoietic stem/progenitor cells (HSPCs) and leukemogenesis, and inhibited all-trans retinoic acid (ATRA)-induced AML cell differentiation; the opposite was true when FTO expression was depleted.(55) Thus, our data demonstrated that FTO plays an essent”
• The potential role of RNA N6-methyladenosine in Cancer progression (2020, background): “FTO was found to promote leukemia oncogene-mediated cell transformation and leukemia, inhibit the differentiation of AML cells induced by all-trans retinoic acid (ATRA), and regulate the expression of its target genes, such as ankyrin repeat and SOCS box containing 2 (ASB2) and retinoic acid recepto”
• m6A RNA methylation: from mechanisms to therapeutic potential (2021, positive): “Loss of METTL14 increases the proliferation and tumorigenicity of endometrial cancer cells by altering the mRNA stability and translation of AKT pathway regulators (Liu et al , 2018). m 6 A has also been reported to play tumor suppressor roles in renal cell carcinoma (Li et al , 2017b).”