Journal
NATURE COMMUNICATIONS
Volume 5, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ncomms6212
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Funding
- Chinese Academy of Sciences [XDA01010404]
- National Basic Key Research Program of China [2014CB910601, 2014CB910604, 2012CB910104, 2011CBA01103]
- National Nature Science Foundation of China [31171358, 31371429, 81372148, 31071257]
- Chinese Government '1000 Youth Talent Program'
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Aberrant expression of Lin28 and let-7 has been observed in many human malignancies. However, its functions and underlying mechanisms remain largely elusive. Here we show that aberrant expression of Lin28 and let-7 facilitates aerobic glycolysis, or Warburg effect, in cancer cells. Mechanistically, we discover that Lin28A and Lin28B enhance, whereas let-7 suppresses, aerobic glycolysis via targeting pyruvate dehydrogenase kinase 1, or PDK1, in a hypoxia-or hypoxia-inducible factor-1 (HIF-1)-independent manner, illustrating a novel pathway to mediate aerobic glycolysis of cancer cells even in ambient oxygen levels. Importantly, we further demonstrate that PDK1 is critical for Lin28A- and Lin28B-mediated cancer proliferation both in vitro and in vivo, establishing a previously unappreciated mechanism by which Lin28/let-7 axis facilitates Warburg effect to promote cancer progression. Our findings suggest a potential rationale to target PDK1 for cancer therapy in malignancies with aberrant expression of Lin28 and let-7.
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