R-2-hydroxyglutarate attenuates aerobic glycolysis in leukemia by targeting the FTO/m⁶A/PFKP/LDHB axis.

ABSTRACT: R-2-hydroxyglutarate (R-2HG), a metabolite produced by mutant isocitrate dehydrogenases (IDHs), was recently reported to exhibit anti-tumor activity. However, its effect on cancer metabolism remains largely elusive. Here we show that R-2HG effectively attenuates aerobic glycolysis, a hallmark of cancer metabolism, in (R-2HG-sensitive) leukemia cells. Mechanistically, R-2HG abrogates fat-mass- and obesity-associated protein (FTO)/N⁶-methyladenosine (m⁶A)/YTH N⁶-methyladenosine RNA binding protein 2 (YTHDF2)-mediated post-transcriptional upregulation of phosphofructokinase platelet (PFKP) and lactate dehydrogenase B (LDHB) (two critical glycolytic genes) expression and thereby suppresses aerobic glycolysis. Knockdown of FTO, PFKP, or LDHB recapitulates R-2HG-

SUBMITTER: Qing Y 

PROVIDER: S-EPMC7935770 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature