PMID- 25301052
OWN - NLM
STAT- MEDLINE
DCOM- 20151124
LR  - 20220409
IS  - 2041-1723 (Electronic)
IS  - 2041-1723 (Linking)
VI  - 5
DP  - 2014 Oct 10
TI  - Lin28/let-7 axis regulates aerobic glycolysis and cancer progression via PDK1.
PG  - 5212
LID - 10.1038/ncomms6212 [doi]
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.
FAU - Ma, Xiaoyu
AU  - Ma X
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Li, Chenchen
AU  - Li C
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Sun, Linchong
AU  - Sun L
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Huang, De
AU  - Huang D
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Li, Tingting
AU  - Li T
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - He, Xiaoping
AU  - He X
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Wu, Gongwei
AU  - Wu G
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Yang, Zheng
AU  - Yang Z
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Zhong, Xiuying
AU  - Zhong X
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Song, Libing
AU  - Song L
AD  - State Key Laboratory of Oncology in Southern China and Department of Experimental 
      Research, Sun Yat-sen University Cancer Center, Guangzhou 510060, China.
FAU - Gao, Ping
AU  - Gao P
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
FAU - Zhang, Huafeng
AU  - Zhang H
AD  - Institute for Cancer Research and CAS Key Laboratory of Innate Immunity and 
      Chronic Disease, Innovation Center for Cell Biology, School of Life Science, 
      University of Science and Technology of China, Hefei 230027, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20141010
PL  - England
TA  - Nat Commun
JT  - Nature communications
JID - 101528555
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (LIN28B protein, human)
RN  - 0 (MicroRNAs)
RN  - 0 (PDK1 protein, human)
RN  - 0 (Pyruvate Dehydrogenase Acetyl-Transferring Kinase)
RN  - 0 (RNA-Binding Proteins)
RN  - 0 (mirnlet7 microRNA, human)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Cell Line, Tumor
MH  - Disease Progression
MH  - *Glycolysis
MH  - Humans
MH  - Hypoxia-Inducible Factor 1, alpha Subunit/genetics/metabolism
MH  - MicroRNAs/genetics/*metabolism
MH  - Neoplasms/genetics/*metabolism/pathology
MH  - Oxygen/metabolism
MH  - Protein Serine-Threonine Kinases/genetics/*metabolism
MH  - Pyruvate Dehydrogenase Acetyl-Transferring Kinase
MH  - RNA-Binding Proteins/genetics/*metabolism
EDAT- 2014/10/11 06:00
MHDA- 2015/12/15 06:00
CRDT- 2014/10/11 06:00
PHST- 2014/03/20 00:00 [received]
PHST- 2014/09/09 00:00 [accepted]
PHST- 2014/10/11 06:00 [entrez]
PHST- 2014/10/11 06:00 [pubmed]
PHST- 2015/12/15 06:00 [medline]
AID - ncomms6212 [pii]
AID - 10.1038/ncomms6212 [doi]
PST - epublish
SO  - Nat Commun. 2014 Oct 10;5:5212. doi: 10.1038/ncomms6212.