R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling.

  title={R-2HG Exhibits Anti-tumor Activity by Targeting FTO/m6A/MYC/CEBPA Signaling.},
  author={Rui Su and Lei Dong and Chenying Li and Sigrid Nachtergaele and Mark E. Wunderlich and Ying Qing and Xiaolan Deng and Yungui Wang and Xiaocheng Weng and Chao Hu and Mengxia Yu and Jennifer R Skibbe and Qing Dai and Dongling Zou and Tong Wu and Kangkang Yu and Hengyou Weng and Huilin Huang and Kyle Ferchen and X D Qin and Bin Zhang and Jun Qi and Atsuo T. Sasaki and David R. Plas and James E. Bradner and Min-jie Wei and Guido Marcucci and Xi Jiang and James C. Mulloy and Jie Jin and Chuan He and Jianjun Chen},
  volume={172 1-2},
R-2-hydroxyglutarate (R-2HG), produced at high levels by mutant isocitrate dehydrogenase 1/2 (IDH1/2) enzymes, was reported as an oncometabolite. We show here that R-2HG also exerts a broad anti-leukemic activity in vitro and in vivo by inhibiting leukemia cell proliferation/viability and by promoting cell-cycle arrest and apoptosis. Mechanistically, R-2HG inhibits fat mass and obesity-associated protein (FTO) activity, thereby increasing global N6-methyladenosine (m6A) RNA modification in R… CONTINUE READING
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