TY - JOUR
T1 - Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1
AU - Ma, Xiaoyu
AU - Li, Chenchen
AU - Sun, Linchong
AU - Huang, De
AU - Li, Tingting
AU - He, Xiaoping
AU - Wu, Gongwei
AU - Yang, Zheng
AU - Zhong, Xiuying
AU - Song, Libing
AU - Gao, Ping
AU - Zhang, Huafeng
N1 - Funding Information:
We are grateful to Dr Chi Van Dang in Abramson Cancer Center of the University of Pennsylvania for his critical reading and suggestions on this manuscript. Our work is supported in part by Chinese Academy of Sciences (XDA01010404), National Basic Key Research Program of China (2014CB910601, 2014CB910604, 2012CB910104 and 2011CBA01103) and National Nature Science Foundation of China (31171358, 31371429, 81372148 and 31071257). H.Z. is supported by Chinese Government ‘1000 Youth Talent Program’.
Publisher Copyright:
© 2014 Macmillan Publishers Limited.
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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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U2 - 10.1038/ncomms6212
DO - 10.1038/ncomms6212
M3 - Article
C2 - 25301052
AN - SCOPUS:84923025327
SN - 2041-1723
VL - 5
JO - Nature communications
JF - Nature communications
M1 - 5212
ER -