FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N 6 -Methyladenosine RNA Demethylase

Zejuan Li, Hengyou Weng, Rui Su, Xiaocheng Weng, Zhixiang Zuo, Chenying Li, Huilin Huang, Sigrid Nachtergaele, Lei Dong, Chao Hu, Xi Qin, Lichun Tang, Yungui Wang, Gia Ming Hong, Hao Huang, Xiao Wang, Ping Chen, Sandeep Gurbuxani, Stephen Arnovitz, Yuanyuan LiShenglai Li, Jennifer Strong, Mary Beth Neilly, Richard A. Larson, Xi Jiang, Pumin Zhang, Jie Jin, Chuan He, Jianjun Chen

Research output: Contribution to journalArticlepeer-review

558 Scopus citations

Abstract

N 6 -Methyladenosine (m 6 A) represents the most prevalent internal modification in mammalian mRNAs. Despite its functional importance in various fundamental bioprocesses, the studies of m 6 A in cancer have been limited. Here we show that FTO, as an m 6 A 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 m 6 A levels in these mRNA transcripts. Collectively, our study demonstrates the functional importance of the m 6 A methylation and the corresponding proteins in cancer, and provides profound insights into leukemogenesis and drug response.

Original languageEnglish (US)
Pages (from-to)127-141
Number of pages15
JournalCancer Cell
Volume31
Issue number1
DOIs
StatePublished - Jan 9 2017
Externally publishedYes

Keywords

  • AML
  • ASB2
  • ATRA
  • cell differentiation
  • FTO
  • leukemogenesis
  • m6A
  • RARA
  • RNA modification
  • RNA stability

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Fingerprint

Dive into the research topics of 'FTO Plays an Oncogenic Role in Acute Myeloid Leukemia as a N <sup>6</sup> -Methyladenosine RNA Demethylase'. Together they form a unique fingerprint.

Cite this