| Literature DB >> 28017614 |
Zejuan Li1, Hengyou Weng2, Rui Su3, Xiaocheng Weng4, Zhixiang Zuo5, Chenying Li6, Huilin Huang3, Sigrid Nachtergaele7, Lei Dong3, Chao Hu8, Xi Qin3, Lichun Tang9, Yungui Wang8, Gia-Ming Hong10, Hao Huang10, Xiao Wang7, Ping Chen10, Sandeep Gurbuxani11, Stephen Arnovitz10, Yuanyuan Li10, Shenglai Li10, Jennifer Strong3, Mary Beth Neilly10, Richard A Larson10, Xi Jiang2, Pumin Zhang9, Jie Jin12, Chuan He13, Jianjun Chen14.
Abstract
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 leukemogenesis and drug response.Entities:
Keywords: AML; ASB2; ATRA; FTO; RARA; RNA modification; RNA stability; cell differentiation; leukemogenesis; m6A
Mesh：
Substances：
Year: 2016 PMID： 28017614 PMCID： PMC5234852 DOI： 10.1016/j.ccell.2016.11.017
Source DB: PubMed Journal: Cancer Cell ISSN： 1535-6108 Impact factor: 31.743